Spanish Society of Cardiovascular & Endovascular Surgery registry of interventions in patients with congenital heart disease: 2021, and retrospective of the previous decade

The Spanish Society of Cardiovascular & Endovascular Surgery presents the 2012-2021 report of the activity in congenital cardiovascular surgery, based on a voluntary and anonymous registration involving most of Spanish centres. This article is complementary to the 2021 cardiovascular surgery annual report, and they are published together. In 2021, still marked by the aftermath of the COVID-19 pandemic, the decline in our 2020 congenital activity persists, compared with previous years. We included data from the previous 10 years, in order to obtain real information related to our activity with these relatively scarce pathologies. In the last decade, a total of 20,139 congenital heart surgeries were performed, accounting for 9.5% of all major surgery (congenital + acquired) performed in Spain during that period. Of these surgeries, 81.5% of them required extracorporeal circulation and 18.5% not. We highlight the interventions in neonates and adult patients, which mean respectively 18% and 21% of our whole activity and are a real challenge. The most prevalent congenital heart pathologies operated on were: septal defects in cases requiring extracorporeal circulation, and ductus in patients without extracorporeal circulation. The presented data are adjusted to the basic Aristotle score of preoperative surgical risk. The observed mortality of surgeries with extracorporeal circulation was 3.07% (Aristotle: 6.29), and without cardiopulmonary bypass 2.25% (Aristotle: 4.82). Our national registry of surgical activity in congenital heart disease shows good results, allows us to compare ourselves within a national and international framework, design improvement strategies, set objectives and improve the quality of our actions.Copyright © 2023 Sociedad Espanola de Cirugia Cardiovascular y Endovascular

PPP1R13L-Related Cardiomyopathy Stability Following IL1 Inhibition

Introduction: Variants in PPP1R13L are associated with severe childhood-onset cardiomyopathy resulting in rapid progression to death or cardiac transplantation. PPP1R13L is proposed to encode a protein that limits the transcriptional activity of the NFkappaB pathway leading to elevated IL-1, IL-6, and TNF-alpha production in murine models. Optimal medical management for PPP1R13L-related cardiomyopathy is unknown. Here we report usage of a targeted anti-IL-1 immuno-modulatory therapy resulting in cardiac stabilization in a pediatric patient with congenital cardiomyopathy secondary to PPP1R13L variants. Case Report: A 4-year-old boy presented acutely with fever in the setting of persistent abdominal pain, vomiting, fatigue, and decreased appetite for two months following a mild COVID-19 related illness. Echocardiogram revealed severely depressed biventricular systolic function with an ejection fraction of 30%. Due to acute decompensated heart failure symptoms with hemodynamic instability, he was intubated and placed on continuous inotropic infusions with aggressive diuresis. Cardiac MRI demonstrated extensive subepicardial to near transmural fibrosis by late gadolinium enhancement in right and left ventricles. An implantable cardioverter-defibrillator (ICD) was placed due to frequent runs of polymorphic non-sustained ventricular tachycardia. Testing for viral pathogens was positive for rhino/enterovirus. Initial genetic testing was non-diagnostic (82-gene cardiomyopathy panel) but given the patient's significant presentation whole genome sequencing was pursued that showed two separate PPP1R13L variants in trans (c.2167A>C,p.T723P and c.2179_2183del,p. G727Hfs*25, NM_006663.4). Patient serum cytokine testing revealed elevations in IL-10 (4.7 pg/mL) and IL-1beta (20.9 pg/mL). Given the patient's tenuous circumstances and concern for continued progression of his cardiac disease, a trial of IL-1 inhibition via anakinra dosed at 3 mg/kg or 45 mg daily was initiated following hospital discharge. With approximately 6 months of therapy, the patient's cardiac function is stable with normalization of IL-10 and IL-1beta serum levels. Notably, the ventricular arrhythmia decreased after initiation of anakinra with no ICD shocks given. Therapy overall has been well tolerated without infectious concerns. Conclusion(s): In patients with PPP1R13L-related cardiomyopathy, immuno-modulatory therapies should be considered in an attempt to slow cardiac disease progression.Copyright © 2023 Elsevier Inc.

Presence of rare potential pathogenic variants in subjects under 60 years old with very severe or fatal COVID-19

Background/Objectives: Genetic variants affecting host defense against pathogens may help explain COVID-19 fatal outcomes. Our aim was to identify rare genetic variants related to COVID-19 severity in a selected group of patients under 60 years who required intubation or resulting in death. Method(s): Forty-four very severe COVID-19 patients were selected from the Spanish STOP-Coronavirus cohort, which comprises more than 3,500 COVID-19 patients. Genotype was performed by whole exome sequencing and variants were selected by using a gene panel of 867 candidate genes (immune response, primary immunodeficiencies or coagulation, among other). Variants were filtered, priorized and their potential pathogenicity was assessed following ACGM criteria. Result(s): We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic (26%). Mostly, the candidate variants were located in genes related to immune response (38%), congenital disorders of glycosylation (14%) or damaged DNA binding genes (9%). A network analysis, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks enriched in carbohydrate metabolism and in DNA metabolism and repair processes. Conclusion(s): The variants identified affect different, but interrelated, functional pathways such as immune response and glycosylation. Further studies are needed for confirming the ultimate role of the new candidate genes described in the present study on COVID-19 severity.

Congenital miliaria crystallina in a neonate of a COVID- 19 positive mother

Introduction: Miliaria crystallina occurring during neonatal period is one of the differential diagnosis for vesiculopustular lesions in that age group. Congenital miliaria crystallina is a rare condition developing due to various causes. Case Report: An otherwise well, term female neonate born by caesarean section presented with generalised clear fluid filled vesicles over the trunk, upper limbs, face and scalp at birth. Mother was COVID-19 positive with fever and cough for 1 week. Otherwise she had an unremarkable antenatal, sexual history and examination. The vesicles were located on normal looking skin and ruptured easily on rubbing. Palms, soles and mucosae were normal. Tzanck smear from the vesicles showed a few deformed keratinocytes only. Venereal Disease Research Laboratory test in dilution for both mother and child was non-reactive. Baby's RT-PCR came negative. She fared well on follow up, the vesicles started to desquamate on the second day and completely disappeared on the third day. Mother's COVID-19 symptoms also subsided after child birth. A final diagnosis of congenital miliaria crystallina was made based on the characteristics of the vesicles. Discussion(s): Miliaria crystallina is triggered by environmental temperature and humidity. Congenital cases are associated with maternal febrile illnesses. However, there are reports of it occurring in newborns of mothers without fever in whom other factors are involved. This is the first report of congenital miliaria crystallina occurring in a neonate born to a COVID-19 positive mother. Conclusion(s): This case report highlights the importance of recognizing this benign self-limiting condition so as to avoid unnecessary investigations to find an alternative cause.

Monkeypox (mpox) is a new problem on a global scale for humanity.

Purpose - to draw attention to an infection that was little known, but has now become a global problem for society;to familiarize readers with the peculiarities of the 2022 monkeypox outbreak and to increase the level of alertness of doctors to this disease. Monkeypox is a global problem because the disease is spreading rapidly, covering 111 countries. Three cases were diagnosed in Ukraine. It is predominantly a self-limited infection, but there are severe and deadly complications. The lethality of this disease ranges from 0% to 11%. The course of the disease is more severe in children and people with reduced immunity. Vertical transmission of the virus from mother to child is possible, resulting in congenital monkeypox. Monkeypox is a zoonotic disease and its natural reservoir is not exactly known, but rodents are most likely to act. In most cases, person-to-person transmission of the virus occurs through close skin to skin contact, often during sexual intercourse. At the beginning of the outbreak 98% of cases of disease were was diagnosed in homo- and bisexuals. Airborne transmission is also possible. Infection is possible through close contact with infectious skin lesions. Clinically, the initial period resembles influenza, but lymphadenopathy is characteristic, which is considered a pathognomonic symptom of mpox. The rash is similar to that of chickenpox, but with more prevalent location on palms and soles than in chickenpox. In the presence of a vesicular rash in a patient, it is necessary to exclude monkeypox. PCR diagnostics of the virus in samples of vesicles or crusts has the greatest diagnostic value. Hygienic skin care is important. Antiviral drugs (tecovirimat, brincidofovir) are recommended only in severe cases. To reduce the spread of infection, international rules apply as for other infections, such as COVID-19. The monkeypox virus vaccine is recommended primarily for groups at risk of infection, including medical personnel who may come into contact with the patient or samples for laboratory testing. Being aware for this infection, following international health regulations, it is possible to prevent the further spread of monkeypox.Copyright © 2023 Tomsk State University. All rights reserved.

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.

ECMO for the immunocompromised pediatric patient: Our experience

Objectives: To present a series of immunosuppressed patients (oncohematological disease, congenital immunosuppression, hematopoietic stem cell (HSCT), and solid organ transplant) assisted on ECMO. Method(s): Descriptive, retrospective study (2011-2020) of a cohort of 9 immunosuppressed patients, supported on ECMO. Medical records were reviewed and demographic, clinical, and analytical variables were collected. Result(s): In our series of 9 patients, 5 were male, the median age was 8 years [RIC 3-11 years]. Considering the underlying disease, 6 were oncologic, 1 liver transplant and 2 with congenital immunodeficiency after HSCT. 4 were under active chemotherapy (median 6 days after the last cycle [RIC 5-188]). 6 were admitted due to acute respiratory failure, 3 due to hemodynamic instability (3/9), (one septic shock). The median PEEP was 12 [RIC 9-15] and FiO2 100% (81-100%). 78% (6) required vasoactive drugs (median inotropic score 35 [RIC 0-75]. 40%. 5 had severe neutropenia and/or plateletopenia in the 24 hours prior to ECMO, and alterations in acid-base balance (median pH 7. 1 [RIC 6.9-7.15]. 5 were on multiorgan failure. TPrimary ECMO transport was performed in 4 patients (44%). Cannulation was peripheral in 80% (57% cervical, 43% femoral) and central in 20%;70% VA-ECMO. Median time of assistance was 15 days [RIC 3.5-31.5] in cardiac ECMO (4), and 29 days [RIC 13.5-42] and in pulmonary ECMO (n=5). The median total time of admission was 45 days [RIC 27-59]. 9 had an infection, 2 COVID after HSCT, and 8 bleeding complications, but only one required surgical revision. Renal replacement therapy was used in 5 (median 9 days [RIC 5-34.5]). Other therapies used were polymyxin hemadsorption(2), intratracheal surfactant(2), plasma exchange(1), infusion of mesenchymal cells(1) and specific memory T lymphocytes(2). 4 patients died, 5 survived decannulation, 2 died later, with an overall survival rate to hospital discharge of 33% (3/9). Conclusion(s): Despite having a worse prognosis, ECMO can increase survival in immunosuppressed patients, in situations that are challenging and require a multidisciplinary approach.

Mistakes and complications in the diagnosis and treatment of children with organic foreign body aspiration

The reason for the publication of this article was the increase in the number of children with long-standing organic foreign bodies in the respiratory tract, the late diagnosis of which causes severe complications. The article presents the three most significant cases from the general series, when the diagnosis and treatment tactics at the stages of treatment were associated with errors both at the prehospital stage and in the hospital. In the first clinical case, as it turned out, the child had aspired multiple foreign bodies. The first bronchoscopy revealed one solid foreign body. Due to severe fibrinous-purulent endobronchitis and contact bleeding, the bronchoscopy procedure was aborted. However, after 10 days, the child independently coughed up the second seed, which was a surprise to us. Control bronchoscopy after 3 weeks revealed no foreign bodies. In the second clinical observation, a child developed bronchiectasis due to a long stay of a foreign body in the respiratory tract. The third case demonstrates the diagnosis and treatment tactics in a child with a foreign body against the background of a coronavirus infection. In the first and third cases, the results of treatment were satisfactory. In the second case, a long stay of peanuts in the respiratory tract led to bronchiectasis in the lower lobe of the left lung, which required its removal. In the follow-up, there are no complaints, the child grows and develops according to age. The study analyzes the mistakes made at the stages of diagnosis and treatment of children with foreign bodies in the respiratory tract. Conclusion. Young children with long-term and atypically current respiratory diseases, dubious and even normal radiological picture with the absence of comprehensive information on the anamnesis of diseases should alert the doctor to the possibility of aspiration of a foreign body in the respiratory tract and serve as the basis for performing bronchoscopy.Copyright © 2023 National Academy of Pediatric Science and Innovation. All rights reserved.

Use of viscoelastic tests in the intensive care unit for the evaluation of haemostasis in SARS-CoV-2 infection

Introduction: COVID-19 coagulopathy is associated with poor prognosis and a state of coexisting 'hypercoagulopathy' (HyperC) and hypofibrinolysis, only detected by viscoelastic tests (VET). VET technology has been useful in areas where conventional tests are inadequate, such as screening for HyperC, thrombotic risk assessment and systemic anticoagulants' effect. We aim to characterize the evolution profile of coagulopathy in patients with COVID-19 infection during their intensive care unit (ICU) stay. Method(s): Consecutive recruitment of adult COVID-19 patients admitted to our hospital's ICU, during a 6 months period. Patients with thrombosis in the previous 3 months, pregnancy, under hormone therapy, and congenital coagulopathies were excluded. VET were executed every 5 days, at discharge and in complications and all of them were under low weight molecular heparin (LMWH) therapy. Group 1 (G1), n = 24-less than 10 days in ICU and group 2 (G2), n = 16-more than 10 days in ICU. In G1 there was 1 death (day 3) and in G2 there were 5 deaths (between days 15 and 42). We focused current analysis on VET-Rotem parameters (see Fig. 1). Result(s): Prognostic scores APACHE II, SAPS II and SOFA were higher in G2, but surprisingly G1 patients are more obese. G2 patients had shorter aPTT and lower platelets. The variables CT-HepTem and MCF Extem-MCF-Fib-Tem present a greater difference between groups, but no statistical significance. We observed an initial correlation between basophils number (which is lower) on CT Intem and CT Hep-Tem, lost as progression to cure, probably due to cytoplasm heparin granules. As expected, VET were in accordance with HyperC: short CTs, increased MCFs, and decreased lysis. Conclusion(s): We expected to guide/adjust LMWH dosage, using Rotem profiles, however these were not corrected by LMWH, used transversally, and remained unchanged in all patients during their stay in ICU.

Study on the risk signal mining related to lopinavir/ritonavir based on the US FDA Adverse Event Reporting System.

Objective: To explore the clinical safety of lopinavir/ritonavir (LPV/r) by mining the risk signals of adverse events (AEs) related to LPV/r for the safe application of the drug in the treatment of novel coronavirus pneumonia (COVID-19). Method(s): The risk signals related to LPV/r in AE reports of US FDA Adverse Event Reporting System (FAERS) from the first quarter of 2010 to the third quarter of 2019 were mined by reporting odds ratio (ROR). An AE with reports more than 3 and 95% confidence interval (CI) lower limit of ROR greater than 1 was defined as a positive signal. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA). The PTs of top 50 adverse event reports and signal strength were selected and analyzed. Result(s): From the first quarter of 2010 to the third quarter of 2019, a total of 13 335 AE reports with LPV/r as the primary suspicious drug were reported in the FAERS database. Four hundred and fifty-five AE risk signals with reports more than 3 and the 95%CI lower limit of ROR greater than 1 were detected, involving 7 718 AE reports. The top 2 system organs involved in AE reports were "injury, poisoning and procedural complications" [13.6% (1 051/7 718)] and "pregnancy, puerperium and perinatal conditions" [11.7% (899/7 718)]. However, 998 (95.0%) of 1051 AE reports involved in "injury, poisoning and procedural complications" were related to drug exposure during pregnancy. The system organ with the highest signals was "congenital, familial and genetic disorders" [16.3% (74/455)]. In addition, 144 AEs caused by drug interactions were detected, which ranked the 7th in the AE reports. Conclusion(s): The risk signals of fetal, neonatal and infant abnormalities related to LPV/r during pregnancy were detected, suggesting that attention should be paid to the risk of using LPV/r in pregnant women and infants. The interaction between LPV/r and other drugs was also worthy of attention.Copyright © 2020 by the Chinese Medical Association.

A nontraumatic, right-sided diaphragmatic hernia in an adult diagnosed during an asthma attack

Case report We present a rare case of a right-sided diaphragmatic herniation of the ascending colon, in a 76-year-old asthmatic patient with a non-congenital diaphragmatic hernia, no history of trauma, surgery, or radiation. The patient presented at the emergency room with dyspnea, non-productive cough, wheezing, tachypnea, tight chest, respiratory failure. This patient has a 40-year history of severe persistent extrinsic asthma, treated with high doses of inhaled corticosteroids and LABA. Before the pandemic, this patient was hospitalized 3-4 times a year for her asthma attacks, but in the last 2 years, due to Covid-19, the patient was not hospitalized, resulting in uncontrolled asthma with daily symptoms. During the hospitalization, chest radiography was performed where the hernia was suspected and confirmed by a CT Scan. Despite the diagnosis of diaphragmatic herniation, she was clinically better with the proper asthma treatment and after consulting with her family she refused the intervention to correct the hernia. She has had two vaginal deliveries, no malignancies, no trauma, no intervention in her life. In this case, the only possible cause for the herniation of the colon is persistent cough combined with advanced age, chronic steroid use, and obstructive lung disease. Non-traumatic, right-sided diaphragmatic hernia of the colon in adults is very rare. Persistent cough with other predisposing conditions of this patient is the cause of this herniation. The chest X-ray and CT were essential for making the diagnosis. Rare hernias like this should be kept in mind when coming to a diagnosis.

Features of COVID-19 in patients with congenital antibody deficiency

Background: Congenital/primary immunodeficiency (PID) affects about 6 million people worldwide, about 50% of whom are antibody deficient. During the COVID-19 pandemic, these people are at special risk because they have inborn errors of immunity and immune defense against infections. A number of immune mediators, in particular serum levels of interleukin 6 (IL-6), are closely correlated with severity and mortality from COVID-19. Method(s): The clinical course of COVID-19 and IL-6 levels in 14 patients with PID were studied. The age of patients ranged from 18 to 46 years. Among 14 patients with PID, 5 were diagnosed with common variable immunodeficiency (CVID), 4 with IgG4 deficiency, 4 with X-linked agammaglobulinemia (XLA), and 1 with WHIM syndrome. All patients with PID received replacement immunoglobulin therapy. The control group was randomly selected from 25 patients with COVID-19 without immune deficiency disease. The level of IL-6 was determined by ELISA. Result(s): Among 14 patients with PID, 10 patients (71.4%) had mild COVID-19 and 4 patients (28.57%) had moderate COVID-19. Importantly, all 4 patients with IgG4 deficiency, 1 patient with WHIM syndrome, 3 out of 5 patients with CVID, and 2 out of 4 patients with XLA had mild COVID-19. It should be noted that the clinical course and level of IL-6 in all patients with PID and control group did not differ statistically. Conclusion(s): More than 70% of patients with congenital antibody deficiencies had a mild form of COVID-19. The predominantly mild course of COVID-19 confirms the important role of cellular immunity in protecting against SARS Cov-2. Interestingly, all patients with XLA experienced mild or moderate COVID-19 without elevated IL-6 levels likely due to decreased activity of Bruton tyrosine kinase, which mediates development of a cytokine storm through activation of NF-kappabeta. Mild forms of COVID-19 in XLA may reflect a decrease in cytokine storm, in particular IL-6 production.

Smarte Inclusion - guided through complex tasks with the RehaGoal app.

The mobile application RehaGoal app is presented for people with acquired and congenital brain damage who have difficulties with complex planning tasks. The development of the RehaGoal app was based on the Goal Management Training approach, which focuses on breaking down an overarching goal into sub-goals and manageable steps to achieve them. So far, this approach has been paper-based, which makes it difficult to transfer to everyday life. Therefore, the RehaGoal app, which can be used on various digital devices such as smartphones, smartwatches, etc., was developed. Our target group often has additional limitations, which is why the RehaGoal app has a barrierfree design, voice output, visual display options, a user-dependent display, simple menu navigation and an authoring system. We illustrate the possible applications of the RehaGoal app with patients in outpatient neuropsychological rehabilitation, during vocational reintegration and during lockdown due to COVID-19.Copyright © Hippocampus Verlag 2023.

Severe Prps1 Deficiency and Response to S-Adenosylmethionine and Nicotinamide Riboside Supplementation

Background: PRPS1 deficiency spectrum is an X-linked condition caused by pathogenic variants in PRPS1, which encodes for the PRPP enzyme involved in the purine synthesis pathway, among other metabolic pathways. Severely affected individuals, also known as Arts syndrome, have congenital sensorineural hearing loss, optic atrophy, developmental delays, ataxia, hypotonia, and recurrent infections. Infections often precipitate worsening of symptoms and many individuals pass away in childhood. Mildly to moderately affected individuals can have isolated hearing loss, also known as DFNX1, or hearing loss with later onset ataxia and optic neuropathy concerns, also known as CMTX5. Given the importance of PRPP in the role of purine synthesis as well as other cellular processes, including formation of NAD(P), supplementation of these pathways is a logical approach for these patients. 2 Arts syndrome patients were previously supplemented with S-adenosylmethionine, starting in mid-childhood, with improvement in infection severity and frequency, as well as stabilization of other symptoms. Recently another Arts syndrome patient was supplemented with S-adenosylmethionine and nicotinamide riboside, starting in early childhood, with improvement in infection frequency and developmental gains. Here we present a now 23 month old male patient with severe PRPS1 deficiency spectrum symptoms, who was started on S-adenosylmethionine and nicotinamide riboside supplementation. Result(s): This is a 23 month old male with developmental delay, retinal dystrophy, congenital bilateral sensorineural hearing loss, and hypotonia with a PRPS1 c.383A > T / p.Asp128Val likely pathogenic variant. He does not have a history of recurrent infections, however family reports relative isolation due to the Covid-19 pandemic. He sat unsupported at 10 months, crawled at 14 months, pulled to stand at 18 months, and is nonverbal. His uric acid testing was in the low range of normal. He had normal purine testing with low normal xanthine and hypoxanthine levels. At 19 months the patient started 20 mg/kg/d S-adenosylmethionine supplementation. At 20 months this was increased to 40 mg/kg/d S-adenosylmethionine and he started on 30 mg/kg/d nicotinamide riboside supplementation. Parents reported subjective improvement in strength and endurance with supplementation. He made significant developmental gains including walking with a walker. He had done well with occasional upper respiratory infections without regression in skills, worsening hypotonia, or increased respiratory needs. Unfortunately, very recently he had a cardiac arrest secondary to respiratory failure from rhinovirus/enterovirus and H. influzenzae pneumonia, for which he remains hospitalized at this time. Conclusion(s): This is the 4th reported patient with severe PRPS1 deficiency treated with S-adenosylmethionine supplementation and the 2nd reported patient treated with nicotinamide riboside supplementation. Both supplements have a limited side effect profile and have a biochemical basis for consideration in PRPS1 deficiency. He initially did well on supplementation with improvements in strength and endurance, as well as developmental gains, however his current trajectory remains to be seen. Unfortunately, NAD/NADP, ADP/ATP, and similar markers were unavailable to us and we plan to continue clinical monitoring on supplementation. Further studies are needed to evaluate the effectiveness of S-adenosylmethionine and nicotinamide riboside supplementation in these patients.Copyright © 2023

CLINICAL CASE OF COVID-19 IN A CHILD WITH A RARE SMITH-LEMLI-OPITZ SYNDROME.

Severe forms of COVID-19 are more likely to develop in children of the first year of life with genetic disorders and congenital malformations. Only a few lethal outcomes of the disease in children have been registered ongoing Worldwide over the entire period of the COVID-19 pandemic. This Article represents a clinical case of COVID-19 in a child with a rare Smith-Lemli-Opitz syndrome. On the 2nd day after the reported contact with a family member with COVID-19 the patient aged 3 years and 2 months old was hospitalized in the infectious diseases department with the diagnoses of <<Severe coronavirus infection (PCR-confirmed);cardiopulmonary insufficiency;and congenital heart disease>>. Since the age of 1.5 months old the patient repeatedly underwent inpatient examination and treatment with the Psycho-Neurological Department of the Belgorod Oblast Regional Children's Clinical Hospital (located in Belgorod, Russia). Furthermore, at the age of 1.5 y/o, according to the results of the medical genetic counseling, the diagnosis of Smith- Lemli-Opitz syndrome was established. Due to the COVID-19, the patient's condition deteriorated rapidly, and on the 5th day after the hospitalization the patient has died due to acute heart failure, cardiogenic pulmonary edema and pulmonary hemorrhage.Copyright © 2023 T.A. Kryuchkova.

Incidences of Adverse Effects of Vaccination against Sars-Cov-2 in Patients with Congenital Coagulopathies

Introduction: Traditionally, the administration of intramuscular vaccination has been avoided in patients with congenital coagulopathies due to its possible deleterious effects, including large hematomas, contractures or fibrosis. However, vaccination against SARS-CoV- 2 received approval from regulatory agencies only for intramuscular administration, since its efficacy by other routes has not been studied, so its administration was generalized by this route in this group of patients. The objective is to evaluate the possible adverse effects secondary to vaccination against COVID-19 in patients diagnosed with congenital coagulopathies in a single center. Method(s): Retrospective, analytical and single-center study documenting the adverse effects of vaccination against COVID-19 in a population diagnosed with congenital coagulopathies in a rural center in Spain. Clinical and epidemiological results were collected. Result(s): Twenty-six patients (61.5% male population) with a median age of 24 years (range 3-79 years) were evaluated. The most frequent congenital coagulopathies were deficiency of factor VII (34.6%), VIII (19.2%) and XI (19.2%). 11.5% received prophylaxis. 20% of the sample was infected during the first wave of the pandemic (pre-vaccination) without the need for hospital admission. The entire sample received vaccination in the complete scheme (3 doses, 57.7% were administered from the Pfizer-Bi brand, the difference from the Moderna-Rec brand) without evidence of significant hemorrhagic or thrombotic complications, presenting the entire sample of humoral immune response. No patient in the sample has required hospital admission secondary to severe COVID-19. Discussion/Conclusion: After completing the vaccination schedule against SARS-CoV-2, it can be inferred that the intramuscular administration of this vaccine does not produce significant hemorrhagic adverse events, being the route of preference at present.

Case report of congenital disorder of glycosylation type Ia combined with dilated cardiomyopathy.

Clinical data and follow-up of a case of congenital disorder of glycosylation type Ia (CDG-Ia) combined with dilated cardiomyopathy admitted to the Department of Cardiology, Children's Hospital of Nanjing Medical University were analyzed retrospectively.The 5-year-old female patient was admitted in December 2016 due to recu-rrent shortness of breath for 2 months.Clinical symptoms and signs included repeated attacks of shortness of breath, physical retardation, malnutrition, binocular esotropia, multiple episodes of hypoglycemia, hepatosplenomegaly, hypotonia and other multi-system damages.Cardiac echocardiography suggested the feature of dilated cardiomyopathy, including the significant enlargement of the left ventricle, and decreased systolic function.Genetic testing revealed a compound heterozygous mutation in the PMM2 gene, and as a result, the patient was diagnosed as CDG-Ia.The patient's condition improved after symptomatic treatments such as Cedilanid, Dopamine, Dobutamine, Furosemide, as well as support treatments like myocardium nutrition, blood sugar maintenance, liver protection, etc.After discharge, the patient was given oral Digoxin, Betaloc, Captopril and diuretics, and hypoglycemia-controlling agents.The patient was followed up every 3-6 months.After more than 2 years of follow-up, the heart function and heart enlargement gradually returned to normal.During the Corona Virus Disease 2019 outbreak, self-withdrawal continued for 2 months.Re-examinations showed decreased cardiac function and enlarged left ventricle again.Medications were resumed again, and the patient was followed up closely.This case report suggested that CDG-Ia may be associated with dilated cardiomyopathy, and the cardiac phenotype may be improved by symptomatic supportive treatment.Copyright © 2021 by the Chinese Medical Association.

Minor Procedures in Patients with Congenital Bleeding Disorders - One Centre Experience

Introduction: Patients with congenital bleeding disorders (CBD) have an increased bleeding tendency, which varies according to the factor deficiency and severity. In most cases, prolonged bleeding is observed after trauma, surgery and/or invasive procedures. Haemostatic treatment is needed to prevent bleeding complications and allow a good clinical outcome. Our aim is to evaluate the management of patients with CBD in minor procedures. Method(s): Retrospective study of patients with CBD who performed minor procedures over a 7-year period, through review of clinical files. Result(s): Between January 2015 and December 2021, 249 minor procedures were performed in 113 patients with CBD: 42 had diagnosis of Haemophilia A (HA) (15 severe without inhibitors;3 severe with inhibitors;4 moderate and 20 mild);12 had Haemophilia B (HB) (7 severe without inhibitors;2 moderate and 3 mild);5 were carriers of HA and 2 of HB. 35 had von Willebrand disease (VWD);15 had rare bleeding disorders (8 FVII deficiency;6 FXI deficiency;1 FX deficiency) and 2 had diagnosis of inherited platelet glycoprotein deficiencies (1 Glanzmann thrombasthenia and 1 Bernard Soulier syndrome). Most procedures were dental treatments (189);synoviorthesis/ infiltration/mesotherapy (17);endoscopies and colonoscopies (15);skin lesions excision (8);COVID-19 vaccination (5);sebaceous cyst excision (4);cardiac catheterization (3);ureteral stent removal (3);bone marrow biopsy (2);cystoscopy (2) and breast fibroadenoma excision (1). Prophylactic treatment was performed in 237 (95%) of the procedures, respectively FVIII concentrate factor (59);FIX concentrate factor (27);DDAVP (66);von Willebrand factor/factor VIII concentrates (44);bypassing agents (24);platelet (6);inactivated human plasma (9);tranexamic acid (47) and epsilon-aminocaproic acid (161). No side effects were reported. Discussion/Conclusion: Most patients that underwent minor procedures had Haemophilia and VDW(83%). The most common procedure was dental treatment (76%). Patients with CBD require attention and special care in dental practice. The haemostatic prophylactic treatment varies according to the specific haemostatic defect, severity and type of procedure. The treatment performed has been demonstrated safe and effective, with low incidences of haemorrhagic and treatment-related complications. These patients' treatment requires multidisciplinary teams and reference centres.

Prevalence and Course of Covid-19 in Patients with Congenital Bleeding Disorders in Russia

Introduction: Published data on the course of COVID-19 in patients with congenital bleeding disorders (CBDs) is limited. There are questions about howCOVID-19 affects the course of CBDs and, conversely, how CBDs affect the course of coronavirus infection? Some authors suggest that patients with CBDs to be less severely affected by COVID-19. The aim of the study: analysis of the prevalence and course of COVID-19 in patients with CBDs in Russia. Method(s): A web-based questionnaire was developed to collect data. The survey was conducted in the period from 25.06.2022 to 31.07.2022. A cluster of 187 patients from different regions and cities of Russia were interviewed. Result(s): The average age of patients was 37 years. The survey group consisted of 144 patients with hemophilia A, 16 with hemophilia B, 24 with vonWillebrand's disease and 1 patient with factor VII deficiency. COVID-19 affected 115 (61.5%) of 187 surveyed patients and 22 (19%) patients suffered from coronavirus infection twice. Hospitalisation was required for 14 (12.3%) patients. At the beginning of the disease, 82 (71%) patients were on prophylactic treatment with the factor concentrates;11 (10%) received therapy with emicizumab, 20 (17%) received therapy with the factor concentrates on demand and 2 (1.7%) received bypass agents. During COVID-19 different types of bleeding were observed in 9 (7.8%) patients: hemarthrosis, ecchymosis, hematomas, epistaxis, menorrhagia, haemorrhoid bleeding. Due to COVID-19 the blood coagulation parameters were monitored for 15 (13%) of 115 patients who had been ill. The haemostatic therapy regimen was changed in 19 (16.5%) patients. Anticoagulant therapy was received by 8 (7%) patients. There were no thrombotic cases. A change in the course of the underlying disease after COVID-19 was noted by 21 (18%) patients, of which 11 noted an increase in joint pain and 9 reported the appearance of pain in previously intact joints. Discussion/Conclusion: The absence of thrombotic complications in patients with CBDs and COVID-19 suggests that hypocoagulability state may be protective against COVID-19 hypercoagulability-related adverse effects. However, the aggravating condition is an increase in joint pain and the involvement of new joints possible due to both hemostatic disorders and autoimmune reaction.

Features and outcomes of adolescent deliveries during COVID-19 pandemic - a bicentric study

Introduction: adolescent pregnancies represent a global public health problem associated with multiple consequences on the well-being of young mothers, their babies and general population. The biggest prevalence of adolescent pregnancies in Europe can be found in southeastern countries. Objective(s): to analyze the features and outcomes of adolescent deliveries during the COVID-19 pandemic. Material(s) and Method(s): retrospective, descriptive study of adolescent mothers delivered in the period 01.01.2020-31.12.2021 in two university medical centers: the Emergency Clinical County Hospital of Arad (Romania), and Clinic of Gynecology and Obstetrics of University Clinical Center of Vojvodina (Serbia). Demographic and anthropometric parameters of adolescent mothers, number and way of delivery, birth weight and Apgar score of neonate, COVID-19 status and data about pathologies and complications associated with pregnancy and delivery were collected from medical records and analyzed statistically using IBM SPSS. Result(s): there were total of 458 adolescent mothers, aged between 12 and 17 (average 16.07+/-1.07 year). From urban environment there were 182 (60.3%) cases and from rural 276 (39.7%) cases. Number of previous pregnancies and births ranged from 0-3, with majority of mothers being primiparas (76.2%). Cesarean section was performed in 40.8%, vaginal birth in 59.2%. The most common indications for cesarean section were maternal-pelvic disproportion, transverse lie or deflected cephalic presentation, twin pregnancies, severe fetal distress, preeclampsia, scarred uterus with risk of rupture and premature placental abruption. The average fetal weight at birth was 3010.22g ranging from 860 to 4500 g. The average Apgar score was 8.73. There were 9.66% of premature labors. There were 9 (2%) positive COVID-19 cases at birth and additional 4 (0.9%) cases who had COVID-19 during pregnancy. We observed a very high percentage (73.86%) of pregnancies without adequate prenatal care. Conclusion(s): Adolescent mothers are prone to develop complications compared to general population. The COVID-19 pandemic might have additional negative influence on the addressability of underage mothers to medical care, this phenomenon being the basis of most complications during pregnancy. Effective interventions, better sexual education and social programs are needed to reduce the number of adolescent mothers and to help them get a much better social reinsertion and an increase in the general quality of life.Copyright © 2023