We should be learning as much from failure as success

'You do not know what you will find, you may set out to find one thing and end up discovering something entirely different'-Alexander Fleming As the pace at which medicine is advancing continues to accelerate, haematologists will increasingly find themselves practising unfamiliar medicine and using novel treatments. Whilst most scientific breakthroughs hopefully lead to an overall improvement in quality of life and prognosis, it is imperative that enough attention is paid to the shortcomings of new treatments and adverse events. The recent COVID-19 pandemic is a stark reminder of the cyclical nature of history and the need for healthcare professionals to utilise lessons learnt by our predecessors. Fleming and the discovery of penicillin highlights how mistakes in practice can sometimes lead to unexpected but useful revelations. The use of thalidomide as a treatment for hyperemesis gravidarum in the 1960s devastatingly lead to birth defects in thousands of people. Today, the repurposing of thalidomide, through lateral thinking and further study, has contributed to significant improvements in the prognosis of patients with Multiple Myeloma.1 Mortality following allogenic stem cell transplant continues to decrease overtime as knowledge surrounding complications and how to manage these improves, despite the fact that patients receiving stem cell transplants are becoming increasingly complex.2 These examples from history demonstrate the merit in studying adverse events and undesired outcomes. National reviews of patient health records indicate that errors currently occur in 10% of hospital admissions.3 With new treatments and more complex patients this will likely increase. It is estimated that voluntary reporting by healthcare professionals of such events only occurs 70% of the time.3 History should be used to guide essential changes in attitudes towards error reporting and help to create an ethos where 'failings' are more willingly recognised as a tool to guide improvement and innovation.

Neurocognitive Outcomes in Congenital Heart Defects Ethics, Evidence, and Vaccination in Pregnancy: Lessons from COVID-19

Among the longstanding problems made vivid by the COVID-19 pandemic are challenges in gathering data to inform the use of vaccines in pregnancy. Although it was known early on that pregnant persons and their offspring faced greater risks of morbidity and mortality from COVID-19 infection, they were excluded from all trials that led to authorization of vaccines. And while reassuring evidence has since been gathered, delays, as well as mixed public health messaging, have led to low uptake of vaccines among pregnant populations, as well as disproportionate burdens for pregnant persons. Dr. Lyerly will consider key ethical issues foregrounded by the COVID-19 response in pregnancy, including the distortions of risk, misaligned incentives, and regulatory challenges. Drawing on results of the NIH-funded PHASES Project, she will describe key conceptual shifts and ethical frameworks that have recently been advanced to better serve the interests of pregnant persons and their offspring facing illness in pandemic and other contexts, as well as specific recommendations for responsible and timely research with this population.

Paxlovid Prophylaxis or Treatment in Pregnancy: Data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry

Background: The US Food and Drug Administration under an Emergency Use Authorization approved use of Paxlovid (nirmatrelavir and ritonavir) for the treatment of mild-to-moderate COVID-19 in adults and children with a positive test for SARS-Co-2 and who are at high risk for progression to severe COVID-19. Pregnant women are at increased risk of severe complications resulting from COVID-19 infection;however, minimal data on the safety of Paxlovid in human pregnancy are available. Objective(s): The objectives of this study are to assess risks of major congenital malformations, spontaneous abortion, elective termination, stillbirth, preterm delivery, small for gestational age infants at birth, or infants who were small for age at one year in pregnancies/infants prenatally exposed to Paxlovid in pregnancy compared to individuals who did not receive this treatment. Design(s): This study involves prospective data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry which enrolls pregnant women residing in the US or Canada and captures data through maternal interviews and ion of medical records. Result(s): Among pregnant women participating in the OTIS Pregnancy Registry as of February 1, 2023, 59 reported exposure to Paxlovid in pregnancy;25.4% exposed within 30 days prior to the last menstrual period and through the first trimester, 42.4% exposed in second trimester, and 32.2% exposed in the third trimester. As of January 2023, 17 of those enrolled have completed pregnancy outcomes. One was lost to follow-up. Of the remainder, there were no adverse pregnancy outcomes reported. Conclusion(s): Very limited data are available on this potentially beneficial treatment in pregnancy. To date, no serious signals for this exposure have been detected.

2022 PeDRA Annual Conference

The proceedings contain 90 papers. The topics discussed include: characterization of nonalcoholic fatty liver disease in children with psoriasis: a pilot study;management of pediatric psoriasis: a representative US survey;severity and patient-related outcomes in atopic dermatitis do not correlate with deprivation index as an indicator of socioeconomic setting in a US metropolitan area;pediatric atopic dermatitis: assessment of burden based on lesional morphology;metered dose applicators: a potential solution for improving topical medication adherence in atopic dermatitis patients;serial staged punch excision technique for linear epidermal nevus and nevus sebaceous;the molecular basis of superficial vascular lesions of the skin: genotype-phenotype correlation of capillary malformations;utilization and effect of telehealth for the treatment of hemangioma before and after COVID;image analysis of port wine birthmarks using optical coherence tomography;image analysis of port wine birthmarks using optical coherence tomography;and responsiveness to change of the morphea activity measure.

Intraorbital lymphatic-venous malformation in an adult patient: is sirolimus the key?

Intraorbital lymphatic-venous malformations are rare lesions that represent a therapeutic challenge given their location and high rate of recurrence, with only a few cases in adult patients having been published in the literature. We present the case of a 30-year-old male with a right intraorbital lymphatic-venous malformation treated with sirolimus at a dose of 4 mg/day with complete clinical and radiologic remission. Mild cold-like symptoms ensued during the first week of treatment and elevation of liver function enzymes and D-dimer occurred in the context of acute SARS-CoV-2 pneumonia. No major adverse effects were documented. After 18 months of treatment, the patient remains asymptomatic and ophthalmologic examinations including optical coherence tomography and visual field test are within normal values.

Fetal impact of cystic fibrosis transmembrane conductance regulator modulator use during assisted and natural reproduction and partner pregnancy in men with cystic fibrosis

Background: Increasing availability of highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapy (HEMT) has improved the quality of life and long-term prognosis for many people with CF. Thus, more people with CF are considering parenthood. Almost all menwith CF (MwCF) are infertile because of congenital bilateral absence of the vas deferens (CBAVD). Based on CF animal models, CBAVD occurs early in gestation and is unlikely to be reversible using HEMT, but assisted reproductive techniques (ARTs) can enable MwCF to father children using the sperm in their testes. Animal reproductive models suggest no HEMT teratogenicity, and the amount of exposure of the fetus to HEMT via absorption of seminal fluid through the vaginal wall is predicted to be negligible, although to ensure no sperm exposure to HEMT, the life span of sperm would require MwCF to discontinue CFTR modulators for approximately 3 months before ART. Because abrupt discontinuation of CFTR modulators may result in health decline, MwCF and their providers must consider all potential risks. There are no published data in MwCF regarding use of HEMT during conception and partner pregnancy. Method(s): Beginning in August 2021, CF center staff in the United States, United Kingdom, and Australia completed a two-page anonymous questionnaire regarding MwCF who used CFTR modulators during ART (sperm retrieval and in vitro fertilization) or natural conception with subsequent partner pregnancy. Result(s): Providers have submitted 34 surveys for MwCF on CFTR modulators whose partner became pregnant after use of ART (n = 32) or natural conception (n = 2). The median age of the samplewas 32 (range 24- 43). Fifteen were homozygous for F508del, median percentage predicted forced expiratory volume in 1 second was 76% (range (22-111%), and median body mass index was 24 kg/m2 (range 18.5-32.1). Twenty-three were taking elexacaftor/tezacaftor/ivacaftor. The median time that MwCF were taking CFTR modulators before partner conception was 18 months (range 0-82). One newly diagnosed man initiated HEMT after sperm retrieval. Four MwCF stopped CFTR modulators before sperm retrieval, one of whom experienced pulmonary decline. None of the 19 MwCF whose condom use during pregnancy was known used condoms. Fetal complications in partners of MwCF included three first-trimester miscarriages, two* COVID, two breech presentation, two* vaginal bleeding, and one vasa previa. None of the complications were deemed definitively related to use of CFTR modulators. One MwCF experienced testicular infection after sperm retrieval#. Postpartum complications included three# infants with hypoxemia requiring neonatal intensive care unit stay, three maternal blood loss, one forceps delivery, and one caesarean section. No congenital anomalies were reported for any infant. (*/# overlap). Conclusion(s): Use of CFTR modulator therapy during partner conception and pregnancy in 34 MwCF has not resulted in higher-than-expected miscarriage rates or congenital anomalies. Providers should consider the risk to the health of MwCF combined with the lack of teratogenicity in animal reproductive models and limited safety data in the human fetus before discontinuing CFTR modulators before ART or natural partner conception. Survey collection is ongoing;results will be updated for presentationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved

REDUCTIONS in STILLBIRTHS and PRETERM BIRTH in COVID-19 VACCINATED WOMEN: A MULTI-CENTRE COHORT STUDY of VACCINE UPTAKE and PERINATAL OUTCOMES

Background: We aimed to measure COVID-19 vaccine uptake among women giving birth in Melbourne and to compare perinatal outcomes by vaccination status. Method(s): Routinely-collected data from all 12 public maternity hospitals in Melbourne were extracted on births >=20 weeks' from 01.07.21 to 31.03.22. Sociodemographic characteristics and perinatal outcomes were compared between COVID-19 vaccinated and unvaccinated women. The primary outcomes were stillbirth and preterm birth in singletons >24 weeks. We calculated the adjusted odds ratio of perinatal outcomes among vaccinated versus unvaccinated women using inverse propensity score weighting regression adjustment with multiple covariates;P < 0.05 was considered significant. Result(s): Births from 32 536 women were analysed: 17 365 (53.4%) were vaccinated and 15 171 (47.6%) were unvaccinated. Vaccination status was significantly associated with multiple sociodemographic factors. Vaccinated women had a significantly lower rate of stillbirth compared with unvaccinated women (0.2% vs. 0.8%, aOR 0.18, 95% CI 0.09- 0.37, P < 0.001). Vaccination was associated with a significant reduction in total preterm births <37 weeks (5.1% vs. 9.2%, aOR 0.60, 95% CI 0.51-0.71, P < 0.001), spontaneous preterm birth (2.4% vs. 4.0%, aOR 0.73 95% CI 0.56-0.96, P = 0.02) and iatrogenic preterm birth (2.7% vs. 5.2%, aOR 0.52, 95% CI 0.41-0.65, P < 0.001). There was no significant increase in congenital anomalies or foetal growth restriction among vaccinated women. Conclusion(s): COVID-19 vaccination during pregnancy was associated with a reduction in stillbirth and preterm birth, and not associated with any adverse impacts on foetal growth or development. Vaccine coverage was significantly influenced by known social determinants of health.

A novel cystic fibrosis-pregnancy service: Two-year review after introduction of elexacaftor/tezacaftor/ivacaftor

Background: As a quality service improvement response since elexacaftor/ tezacaftor/ivacaftor (ELX/TEZ/IVA) became available and the yearly average number of cystic fibrosis (CF) pregnancies (n = 7 pre-2020, n = 33 in 2021) increased significantly at an adult CF center (~600 people with CF), a monthly multidisciplinary CF-maternal health virtual clinic was established with antenatal virtual CF exercise classes dedicated to providing adaptive, specialist support to this cohort, aswell as outreach guidance and education to local obstetric teams. Method(s): This was a single-center retrospective reviewof Royal Brompton Hospital CF-Maternal Health multidisciplinary team clinic records and a patient survey from March 2020 to March 2022. Result(s): Of 47 pregnancies in 41 women (median age 30;) eligible for ELX/ TEZ/IVA at start of pregnancy, 40% (n = 19) were unplanned, and 19% (n = 9) used assisted conception. Three women with a history of infertility conceived naturally, having required assisted conception for previous pregnancies, and five women had multiple pregnancies during the study period. ELX/TEZ/IVA was continued in 60% (n = 28), delayed in 28% (n = 13), and stopped in 13% (n = 6) of pregnancies through maternal choice and careful clinical counselling. Pre-pregnancy pulmonary status was poorer in women who continued than in those who delayed or stopped (Table 1). Of those who stopped, 85% (n = 5) restarted because of pulmonary deterioration by the third trimester. Prenatal CF complications included at least one episode of minor hemoptysis in 21% (n = 9/41) of women, at least one infective exacerbation in 55% of pregnancies (n = 26/47), and noninvasive ventilation in one woman. Other pregnancy-associated complications included one case of ovarian hyperstimulation syndrome, one case of sub-segmental pulmonary embolism, and two cases of pregnancy-induced hypertension. Excluding 10 first trimester terminations, 10 current pregnancies, and one patient relocation, obstetric outcomes available for 26 pregnancies confirmed a live birth rate of 85% (n = 22/26) and a 15% first-trimester miscarriage rate (n = 4). Obstetric complications included preterm delivery rate of 23% (n = 6/26), including two cases of COVID infection resulting in two neonatal intensive care unit admissions, one case of endometritis after cesarean section, and a fourthdegree perineal tear. There were no ectopic pregnancies, maternal or neonatal deaths, or reports of infant cataracts or congenital malformations. Median gestational age was 37/40 weeks (range 29-40). Mode of delivery was via cesarean section in 45% (n = 10/22, of which twowere emergency) and vaginal in 55% (n = 12/22), of which 83% (n = 10/12) were via induction of labor for diabetes (CF or gestational) indication. Deliveries were supported and occurred equally at local obstetric units and in tertiarycare obstetric hospital settings (50%, n = 11/22). Patient-experience survey responses cited high levels of confidence in health optimization and prioritization during pregnancy and praised excellent inter-health care provider communication and peer-to-peer emotional support provided among expectant mothers in the virtual prenatal exercise groups. Table 1. Baseline demographic and clinical characteristics of elexacaftor/tezacaftor/ivacaftoreligible expectant mothers according to therapeutic decision (Table Presented) Conclusion(s): In the absence of clinical trial safety data, the novel approach of a dedicated CF-maternal health multidisciplinary team clinic with local obstetric outreach support has ensured regular specialist clinical and emotional peer-to-peer support for this cohort of women eligible for ELX/ TEZ/IVA to ensure optimal outcomes and experiences of their pregnancies, where appropriate, close to home.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Post-Operative Outcomes in 'Monti' Construction for Neurogenic Bladders in an Adult Population

INTRODUCTION AND OBJECTIVE: Various diversion techniques exist for the management of neurogenic bladders. In pediatrics, the appendicovesicostomy is a successful approach but may not be applicable for all patients. An alternative is the Yang-Monti ("Monti") catheterizable conduit, created using a section of small bowel. Although commonly used in pediatrics, there are very few series evaluating adults. This study aims to evaluate "Monti" outcomes in an adult population. METHOD(S): Between 1999 and 2022, "Monti" procedures at a single institution were identified using CPT codes, and the list was reviewed to select for adult patients with neurogenic bladder dysfunction. Preoperative data included indications for surgery and patient demographics. Perioperative (day 0 to end of hospital stay) data included time to return of bowel function, length of stay, and perioperative complications. Long-term complications included infections, hospital admissions, and reoperations. Data are presented as means or percentages. RESULT(S): 21 adult patients (male n=8;female n=13) with neurogenic bladder dysfunction were identified. 14 patients developed neurogenic bladder secondary to trauma, while other indications for surgery included idiopathic urinary retention (n=1), tumors (n=2), congenital abnormalities (n=2), multiple sclerosis (n=1), and autoimmune neuropathy (n=1). The mean follow-up time was 3.13 years and mean age at surgery was 35.5 years. The mean time to return of bowel function was 2.7 days (n=14) and postoperative hospital stay was 4.3 days (n=16). Perioperative complications occurred in 10 patients (47.6%) in the first 30 days including UTIs (n=3), surgical site infection (n=3), ileus (n=1), small bowel obstruction (n=1), and suprapubic tube related complications (n=3). Five emergency room admissions for urologic concerns occurred within this period with a total of 28 visits overall. At six month follow-up, a total of six (28.6%) patients had longer-term complications. These included a takedown, a scheduled revision, a hospitalization for complicated UTI, and three patients who were unable to catheterize. Overall, nine patients (42.9%) required reoperation, including three revisions and one cystectomy with conversion to ileal conduit. Two patients expired during the course of this study due to COVID pneumonia and suspected sepsis. CONCLUSION(S): "Monti" procedures are useful for adult patients with neurogenic bladder dysfunction. However, these procedures are associated with significant complications. This information should be used to aid in presurgical counseling.

DETECTION AND CLASSIFICATION OF COVID-19 CASES FROM OTHER CARDIOVASCULAR CLASSES FROM ELECTROCARDIOGRAPHY SIGNALS USING DEEP LEARNING AND ResNet NETWORK

Nowadays, the world confronts a highly infectious pandemic called coronavirus (COVID-19) and over 4 million people worldwide have now died from this illness. So, early detection of COVID-19 outbreak and distinguishing it from other diseases with the same physical symptoms can give enough time for treatment with true positive results and prevent coma or death. For early recognition of COVID-19, several methods for each modality are proposed. Although there are some modalities for COVID-19 detection, electrocardiography (ECG) is one of the fastest, the most accessible, the cheapest and the safest one. This paper proposed a new method for classifying COVID-19 patients from other cardiovascular disease by ECG signals. In the proposed method, Resnet50v2 which is a kind of convolutional neural network, is used for classification. In this paper because of image format of data, first data with image format are applied to the network and then for comparison, ECG images are changed to signal format and classification is done. These two strategies are used for COVID-19 classification from other cardiac abnormalities with different filter sizes and the results of strategies are compared with each other and other methods in this field. As it can be concluded from the results, signal-based data give better accuracy than image classification at best performance and it is better to change the image format to signals for classification. The second result can be found by comparing with other methods in this field, the proposed method of this paper gives better performance with high accuracy in COVID-19 classification. Copyright © 2023 National Taiwan University. National Taiwan University.

Impact of SARS-CoV-2 infection in patients with hereditary hemorrhagic telangiectasia: epidemiological and clinical data from the comprehensive Italian retrospective multicenter study.

Rare Disease patients manifested high concern regarding the possible increased risk of severe outcomes and worsening of disease-specific clinical manifestation due to the impact of COVID-19. Our aim was to assess the prevalence, outcomes, and impact of COVID-19 in patients with a rare disease such as Hereditary Hemorrhagic Telangiectasia (HHT) in Italian population. A nationwide, multicentric, cross-sectional observational study was conducted on patients with HHT from five Italian HHT centers by online survey. The association between COVID-19-related signs and symptoms and nosebleeds worsening, the impact of personal protective equipment on nosebleeds pattern, and the relationship between the presence of visceral AVMs and severe outcomes were analyzed. Out of 605 total survey responses and eligible for analysis, 107 cases of COVID-19 were reported. A mild-course COVID-19 disease, not requiring hospitalization, was observed in 90.7% of patients, while the remaining eight cases needed hospitalization, two of them requiring intensive-care access. No fatal outcome was recorded and 79.3% of patients reported a complete recovery. No difference in infection risk and outcome between HHT patients and general population was evidenced. No significative interference of COVID-19 on HHT-related bleeding was found. The majority of patients received COVID-19 vaccination, with relevant impact on symptoms and need for hospitalization in case of infection. COVID-19 in HHT patients had an infection profile similar to the general population. COVID-19 course and outcome were independent from any specific HHT-related clinical features. Moreover, COVID-19 and anti-SARS-CoV-2 measures did not seem to affect significantly HHT-related bleeding profile.

Prevalence of abnormalities on cardiac MRI in unselected patients after recovery from acute SARS-CoV-2 infection and correlation with markers of immunity and coagulation: The SETANTA study

Background: Previous studies have reported ongoing cardiac inflammation as assessed by cardiac magnetic resonance imaging (CMR) in a significant proportion of patients several months after recovery from SARSCoV- 2 infection, many of whom had no or minimal symptoms at the time of infection. Purpose(s): The aim of SETANTA was to investigate the prevalence of cardiac abnormalities by CMR in unselected patients in Ireland after acute SARS-CoV-2 infection and the correlation with immunological response and biomarkers of coagulation. Method(s): This was a prospective, observational, community-based study (clinicaltrials.gov identifier NCT04823182). Consecutive patients recovered from recent SARS-CoV-2 infection at 3 primary care sites were invited to participate. Key inclusion/exclusion criteria and outcomes of interest are shown in Figure 1. Result(s): 100 participants were enrolled (Feb-Sept 2021) at a median of 188 (IQR, 125, 246) days after positive SARS-CoV-2 swab. At index infection, 18% and 35% reported severe and moderate symptoms, respectively;14% were hospitalized;3% were admitted to intensive care for ventilatory support. At enrolment, 83% had ongoing symptoms. 85% had detectable SARS-CoV-2 antigens. CMR and laboratory findings are shown in Figure 1. Conclusion(s): Among an unselected cohort of patients recovered from acute SARS-CoV2 infection, we report a low prevalence of cardiac abnormalities by CMR, despite a high prevalence of moderate/severe symptoms at presentation and a high prevalence of persistent symptoms. Correlation with biomarkers of immunity and coagulation will be available at ESC 2022.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in COVID-19 patients: A systematic review

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening drug-induced condition presenting with skin rash, fever, lymphadenopathy, systemic involvement and hematological (eosinophilia, atypical lymphocytes) findings. Although DRESS syndrome is frequently associated with reactivation of herpesviruses, the link between DRESS and COVID-19 has not been systematically analyzed. Method(s): A systematic search using PubMed and Google Scholar was conducted following the PRISMA guidelines to identify all reported DRESS cases associated with COVID-19 published between January 2020 and January 2022 using the keywords "COVID-19" AND "DRESS syndrome" OR "drug reaction with eosinophilia and systemic symptoms" OR "drug-induced hypersensitivity syndrome" OR "eosinophilia" AND "SARS-CoV- 2" OR "coronavirus". The identified DRESS cases were evaluated using the Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system [Kardaun et al, 2007]. Result(s): We identified twelve published DRESS cases associated with COVID-19 (Table 1). Eleven patients presented with severe COVID-19 disease complicated by DRESS syndrome that developed several days after initial COVID-19 clinical presentation (ARDS n5;multiorgan failure n1;pneumonia requiring mechanical ventilation, n4), one patient was asymptomatic. The culprit drugs included piperacillin-tazobactam (n4), hydroxychloroquine (n5), vancomycin (n2), ceftriaxone (n1), midazolam (n1), sulphasalazine (n1), azithromycin (n1), esomeprazole (n1), cefepime (n1), levofloxacin (n1), and meropenem (n1). The latency between the onset of treatment with culprit drug(s) and the onset of symptoms ranged from 9 to 42 days. All patients presented with widespread maculopapular rash, affecting > 50% of body surface area;five patients also had facial edema. Systemic involvement included liver (n8), renal abnormalities (n8), and heart involvement (n4). All patients had elevated body temperature (fever > = 38.5degreeC, n6) and blood eosinophilia, five patients had lymphadenopathy. Atypical lymphocytes were a rare laboratory finding (n2). Systemic corticosteroids were used in all patients;three patients received benralizumab for DRESS syndrome. Nine patients recovered, two patients died and the outcome was not reported in one case Conclusion(s): DRESS syndrome in COVID-19 patients is associated with multiple drugs, most notably with hydroxychloroquine and a variety of antibiotics. An early recognition may improve management of DRESS syndrome in COVID-19 patients.

Idiopathic anomalous congenital band causing small intestinal obstruction in a 5-month-old dog

A 5-month-old, intact male, yellow Labrador retriever was presented with a 24-hour history of anorexia and vomiting. Abdominal imaging revealed the presence of a mechanical obstruction in the jejunum and peritoneal effusion. Cytologic evaluation and culture of the effusion prior to surgery identified a suppurative exudate with bacteria consistent with septic peritonitis and suspected to be related to the intestinal lesion. An exploratory laparotomy was performed, and a segment of jejunum was circumferentially severely constricted by an off-white, fibrous band of tissue. Resection and anastomosis of the strangulated segment of jejunum and excision of the constricting band provided resolution of the clinical signs. The dog made a complete recovery. Histologic evaluation revealed the band to be composed of fibrovascular and smooth muscle tissue, consistent with an idiopathic anomalous congenital band. No other gastrointestinal lesions were observed, either grossly at surgery or histologically in the resected segment of intestine. To our knowledge, a similar structure has not been reported in the veterinary literature.Copyright © 2022 Canadian Veterinary Medical Association. All rights reserved.

Evaluation of cardiovascular autonomic dysfunction in symptomatic post COVID-19 patients

Background: The COVID-19 disease is known for its severe respiratory complications, however it was found to have some cardiovascular complication in post COVID-19 patients. The heart rate variability (HRV) is a non invasive, objective and reliable method for assessment of autonomic dysfunction in those recovered patients. Purpose(s): We aimed to evaluate the cardiac autonomic function by using valid HRV indices in subjects who recovered from mild to moderate acute COVID-19 but still symptomatic. Method(s): The study Group composed of 50 subjects with confirmed history of mild to moderate post COVID 19. All subjects underwent routine 2D echocardiography assessment in addition to 2D speckle tracking and 24 hours Holter monitoring for HRV analysis. Result(s): The mean age of the study population was 42+/-18 years, symptoms were reported as follows 27 (54%) had Dyspnea, 17 (34%) had palpitations, 7 (14%) had dizziness. Time domain parameters SDNN, SDANN and rMSSD were diminished with mean SDNN value being markedly impaired in 12 (24%) patient, while frequency domain parameters as assessed by LF/HF ratio with mean of 1.837 with 8% of patients being impaired. SDNN was significantly reduced in elderly patients (p=0.001), smokers (p=0.019) and hypertensive (p=0.016) and those complaining mainly of palpitation (p=0.006). SDNN was significantly reduced in patient with impaired LV diastolic function (p=0.009), in patients with reduced MAPSE (p=0.047), reduced TAPSE (p=0.00) and impaired Global longitudinal strain (0.000). Conclusion(s): Patients with post COVID-19 syndrome have abnormalities in the HRV which indicates some degree of dysfunction in the autonomic nervous system and consequently impaired parasympathetic function in this population, however this have been also correlating with subtle impairment of the left ventricular systolic function.We believe that this preliminary research can serve a starting point for future research in this direction.

Adults with congenital heart disease and COVID-19

Background: Adults with congenital heart disease (ACHD) are considered at increased risk for complications due to COVID-19, especially in those with cyanosis or heart failure. However, data regarding the rate of infection as well as regarding a myocardial involvement of a COVID-19 infection in ACHD patients are currently lacking. Purpose(s): To study the rate of COVID-19 infections in ACHD patients from a tertiary centre as well as the rate of myocardial involvement of a COVID- 19 infection. Method(s): All consecutive ACHD patients (over the age of 18 years) who attended the outpatient clinic of a tertiary centre from January 2021 to June 2021 were eligible to participate. Demographic data, as well as medical/ surgical data including a history of a COVID-19 infection were collected. All patients had an antibody test for COVID-19. Patients with a positive antibody test were offered cardiovascular magnetic resonance imaging (CMR). Result(s): Altogether, 420 patients (44.8% female, mean age 36.4+/-11.6 years) were included in the study. Congenital heart defect (CHD) complexity according to the Bethesda classification was simple in 96 (22.9%), moderate in 186 (44.3%), complex in 117 (27.9%), and miscellaneous in 21 (5.0%) patients. A positive antibody test for COVID-19 was present in 28 (6.7%) patients (CHD complexity: Simple n=5, moderate n=14, severe n=7, miscellaneous n=2). Out of these 28 patients, 14 had no symptoms at all. Those with symptoms had mainly mild symptoms and were all managed in the outpatient setting. While 11 patients (39.3%) were not at all aware of their infection, 17 already knew that they had COVID-19. There was no significant difference between ACHD patients with a positive test vs those with a negative test regarding age, gender, New York Heart Association class, or complexity of CHD. Out of the 28 patients with a positive antibody test, 14 agreed to a CMR. A myocardial involvement, i.e. signs of active or healed myocarditis, was not present in any of these. Conclusion(s): In this single-centre study, 6.7% of ACHD patients attending the outpatient clinic had positive antibodies for COVID-19. Out of these, 50% were asymptomatic and 39.3% were not aware of their infection. A myocardial involvement was not found in any of the patients that underwent a CMR. These results indicate a large number of undetected cases of COVID-19 in the ACHD population and offer reassurance that in the vast majority of cases the infection has a mild course.

Fitness and Sports in Children and Adolescents with Congenital Heart Defects during the COVID-19 Pandemic

Background: Physical activity is important for healthy physical and mental development in children and adolescents with congenital heart defects (CHD). The COVID-19 pandemic, which is still ongoing, had an impact on many sports activities. These often could not take place or were limited due to closures, staff shortages and group size restrictions. Method(s): The aim of the study was to learn more about the nutrition and physical activity of young and adolescent CHD patients. CHD patients registered in the German National Register for Congenital Heart Defects were invited by email/postto join the study. In total, 981 patients took part and 894 patients have completed the online questionnaire (average age:12.5 +/- 3 years;47.2% female). CHD severity: 213 simple CHD (23.8%), 338 moderate CHD (37.8%), and 343 complex CHD (38.4%). The study participants were asked to answer questions regarding nutrition, physical activity and (school)sports. Result(s): Subjective fitness level at the time of the survey was rated 6.2 on a scale of 1 (very unfit) to 10 (very fit).Significant differences in subjective fitness levels were present between all three CHD severity groups (p < 0.01): simple CHD 6.8 +/- 2.2;moderate CHD 6.3 +/- 2.2;complex CHD 5.8 +/- 2.2. For 40.7% of the respondents, the physical-sporting fitness has deteriorated during the 1st lockdown in Germany from March 2020 to May 2020 according to their own assessment (no significant differences between CHD severity groups). Also, during the 2nd lockdown in Germany starting in December 2020 until the end of April 2021, physical activity fitness status worsened in 41.5% of cases without significant influence of CHD severity. Overall, 43.8% of respondents reported doing less exercise than before the pandemic, 13.1%reported doing the same amount of exercise, and 43.1% self-reported doing more exercise than before the pandemic (no significant differences between CHD severity groups). Conclusion(s): Overall, the assessment of the own fitness level of young and adolescent CHD patients CHD seems to be dependent on the CHD severity, which is also expected and thus plausible from a medical point of view. The pandemic has a major impact on the sports behavior and decreased the possibility and willingness to participate in (regular) sports. However, the pandemic affects all patients to a similar extent. In the pandemic, it has unfortunately been only partially successful so far to support and encourage young patients to do sports regularly to prevent secondary diseases.

Abnormal echocardiographic findings after COVID-19 infection: A multicenter registry

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has transformed health systems worldwide. There is conflicting data regarding the degree of cardiovascular involvement following infection, generating uncertainty in patients and an additional healthcare burden with increased diagnostic testing. A registry was designed to evaluate the prevalence of echocardiographic abnormalities in Latin American adults recovered from COVID-19. Method(s): We prospectively evaluated 595 participants (mean age 45.5+/-14.9 years;50.8% female) from 10 institutions in Argentina and Brazil. Echocardiographic studies were conducted with General Electric equipment;2DE imaging and global longitudinal strain (GLS) of both ventricles were performed. Comparisons between groups were made with Chisquare, Fisher and Student's t-test. Logistic regression was performed to determine variables associated with abnormal echocardiogram findings. Result(s): A total of 61.7% of the participants denied any relevant cardiovascular medical history. Table 1 summarizes the comorbidities of the included patients. The majority of patients (82.5%) had the disease at home or in an out-of-hospital center. Of the patients who required hospitalization, 15.3% were in a general ward, 1.9% in intensive care and 0.3% required mechanical ventilation during the disease. The median time between infection and performance of the echocardiographic study was two months (IQR 1- 3 months). Among patients who reported symptoms following COVID-19 recovery (41.8%), the most frequently reported was dyspnea (47.4%), followed by mild symptoms such as asthenia, arterial hypertension or palpitations (32.9%), 12.9% referred chest pain, 6% of patients reported dyspnea and chest pain, and 0.8% reported various other symptoms. The mean left ventricular ejection fraction (LVEF) was 61.0+/-5.5% and the mean left atrial volume was 33.1+/-13.2 ml/m2. In patients without prior comorbidities, 8.2% had some echocardiographic abnormality (Figure 1). We found no significant differences in LVEF between symptomatic and asymptomatic patients (61.4% versus 60.6% respectively, p=0.104). Symptomatic patients showed slightly reduced GLS (-20.3% versus -20.9%, p=0.012) with a trend in the same direction in the RV free wall GLS (-25.6% versus -26.3%, p=0.103). Male patients were more likely to have any new echocardiographic abnormalities (OR 2.82, p=0.002). Time elapsed since infection resolution (p=0.245), the presence of symptoms (p=0.927), or history of hospitalization during infection (p=0.671) did not have any correlation with echocardiographic abnormalities. The difference between sexes remains unchanged after adjusting for left atrial volume, wall thicknesses, diastolic function and abnormal wall motion. Conclusion(s): Our results suggest that cardiovascular abnormalities after COVID-19 infection are rare and usually mild, especially in cases of mild disease. These abnormalities may be more frequent among males.

The use of handheld ultrasound device in cardiac examination of patients with history of COVID-19

Background: Clinical usefulness of Handheld Ultrasound Device [HUD] was previously confirmed in numerous clinical scenarios. During the previous two years Covid-19 patients become a focal point of healthcare worldwide. The assessment of long term consequences of this infection is bound to overload already burdened healthcare system. Purpose(s): To assess clinical usefulness of HUD as an adjunct to physical cardiac examination of patients with history of COVID-19. Method(s): Study population consisted of randomly selected patients with no symptoms of cardiovascular pathology, who had been hospitalized due to COVID-19 one year prior to examination. Physical examination and clinical assessment was augmented with short examination with the use of HUD, which included: Visual evaluation of the global and regional LV function, measurement of RV size, screening for the significant valve defects and the presence of pericardial effusion. Subsequently full echocardiographic examination with the use of high-end workstation was performed, which results were treated as reference. Result(s): 54 patients (35 men, mean age 63+/-13 years) were enrolled into the study. In clinical examination no significant cardiovascular abnormalities were discovered. In 30 [56%] of patients cardiac abnormalities in HUD examination were detected. In 18 patients [33%] LV function assessment was not performed, due to insufficient quality of registered view. In the remaining group significant impairment of LV ejection fraction (<50%) was detected in HUD examination in 3 [6%] patients (2 confirmed in full examination, positive predictive value [PPV] 57%, negative predictive value [NPV] 97%, AUC 0,82+/-0,17, P 0,057). WMA were diagnosed in 6 [11%] patients (4 confirmed in full examination, PPV 84% NPV 78%, AUC 0,69+/-0,17, P 0,02). RV enlargement was identified in 21 [39%] patients (PPV 57%, NPV 97%, AUC 0,85+/-0,05, P<0,0001), mild pericardial effusion in 3 [6%] patient (1 confirmed in full echocardiographic examination;2 false positive, no false negative), at least moderate mitral/tricuspid/aortic valve insufficiency in 7 [13%] patients (3 confirmed, 4 false positive cases, no false negative). A total mean time of the heart and lungs HUD examination was 2,1+/-0,6 minute. Conclusion(s): Cardiac abnormalities exposed in brief assessment with the use HUD are a relatively common finding in asymptomatic patients previously hospitalized due to COVID infection in a 1-year follow-up, despite normal physical examination. Normal HUD examination excludes the presence of significant cardiac abnormalities with high probability. However one should keep in mind a relatively high percentage of false positive results, which may lead to an exceeding number of patients referred for a full echocardiographic examination.

Intramedullary spinal cavernous malformations with high ossification: a case report and review of the literature.

BACKGROUND: Cavernous malformations of the spinal cord are a rare type of vascular malformation, comprising approximately 5 to 16% of all vascular lesions in the spinal cord. Depending on their origin position, these malformations can be distributed in different locations within the spinal canal. Although intramedullary cavernous malformations have been reported in the literature, they are exceedingly rare. Furthermore, highly calcified or ossified intramedullary cavernous spinal malformations are even rarer. CASE PRESENTATION: Here, we present a case report of a 28-year-old woman diagnosed with a thoracic intramedullary cavernous malformation. The patient had been experiencing progressive numbness in her distal limbs for a period of 2 months. During routine lung computed tomography screening for COVID-19, a hyperdense mass was noted in the patient's spinal canal. Magnetic resonance imaging revealed a mulberry-shaped intramedullary mass at the T1-2 level. The patient underwent surgical treatment, during which the entire lesion was successfully removed, resulting in a gradual improvement of her symptoms. Histological examination confirmed the presence of cavernous malformations with calcification. CONCLUSIONS: Intramedullary cavernous malformations with calcification are rare and special type that should be treated surgically in the early stage without significant neurological impairment before rebleeding or enlargement of the lesion can occur.