Comparison of Characteristics and Outcomes of Multisystem Inflammatory Syndrome, Kawasaki Disease and Toxic Shock Syndrome in Children.

Background and Objectives: Since the first cases of multisystem inflammatory syndrome in children (MIS-C) in April 2020, the diagnostic challenge has been to recognize this syndrome and to differentiate it from other clinically similar pathologies such as Kawasaki disease (KD) and toxic shock syndrome (TSS). Our objective is to compare clinical signs, laboratory data and instrumental investigations between patients with MIS-C, KD and TSS. Materials and Methods: This retrospective observational study was conducted at the Children's Clinical University Hospital, Latvia (CCUH). We collected data from all pediatric patients <18 years of age, who met the Centers for Disease Control and Prevention case definition for MIS-C, and who presented to CCUH between December 2020 and December 2021. We also retrospectively reviewed data from inpatient medical records of patients <18 years of age diagnosed as having KD and TSS at CCUH between December 2015 and December 2021. Results: In total, 81 patients were included in this study: 39 (48.1%) with KD, 29 (35.8%) with MIS-C and 13 (16.1%) with TSS. In comparison with TSS and KD, patients with MIS-C more often presented with gastrointestinal symptoms (abdominal pain (p < 0.001), diarrhea (p = 0.003)), shortness of breath (p < 0.02) and headache (p < 0.003). All MIS-C patients had cardiovascular involvement and 93.1% of MIS-C patients fulfilled KD criteria, showing higher prevalence than in other research. Patients with KD had higher prevalence of cervical lymphadenopathy (p < 0.006) and arthralgias (p < 0.001). In comparison with KD and TSS, MIS-C patients had higher levels of ferritin (p < 0.001), fibrinogen (p = 0.04) and cardiac biomarkers, but lower levels of platelets and lymphocytes (p < 0.001). KD patients tended to have lower peak C-reactive protein (CRP) (p < 0.001), but higher levels of platelets. Acute kidney injury was more often observed in TSS patients (p = 0.01). Pathological changes in electrocardiography (ECG) and echocardiography were significantly more often observed in MIS-C patients (p < 0.001). Conclusions: This research shows that MIS-C, KD and TSS have several clinical similarities and additional investigations are required for reaching final diagnosis. All the patients with suspected MIS-C diagnosis should be examined for possible cardiovascular involvement including cardiac biomarkers, ECG and echocardiography.

Short- and mid-term outcomes of multisystem inflammatory syndrome in children: a longitudinal prospective single-center cohort study.

Background: Multisystem inflammatory syndrome in children (MIS-c) emerged during the coronavirus disease 2019 pandemic and is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the extensively studied clinical manifestation of acute condition, the short- and long-term effects of MIS-c on children's health are unknown. Methods: This was a prospective longitudinal cohort study. Children aged <18 years who met the Centers for Disease Prevention and Control (CDC) diagnostic criteria and who were admitted to the Children's Clinical University Hospital of Latvia (CCUH) between July 1, 2020, and April 15, 2022, were enrolled in the study. An outpatient follow-up program was initiated in July 2020. All children were evaluated at 2 weeks, 2 months (1-3 months), and 6 months (5-7 months) after discharge. The face-to-face interviews comprised four domains as follows: symptom assessment, physical examination, laboratory testing, and cardiological investigation [including electrocardiogram (ECG) and echocardiography (echo)]. Results: Overall, 21 patients with MIS-c were enrolled. The median age of the study group was 6 years. At the 2-week follow-up, almost half of the patients (N = 10, 47.6%) reported exercise intolerance with provoked tiredness. Laboratory tests showed a considerable increase in blood cell count, with a near doubling of leukocyte and neutrophil counts and a tripling of thrombocyte levels. However, a decline in the levels of inflammatory and organ-specific markers was observed. Cardiological investigation showed significant improvement with gradual resolution of the acute-phase pathological findings. Within 2 months, improvement in exercise capacity was observed with 5-fold and 2-fold reductions in physical intolerance (N = 2, 9.5%) and physical activity-induced fatigue (N = 5, 23.8%), respectively. Normalization of all blood cell lines was observed, and cardiological investigation showed no persistent changes. At the 6-month visit, further improvement in the children's exercise capacity was observed, and both laboratory and cardiological investigation showed no pathological changes. Conclusions: Most persistent symptoms were reported within the first 2 weeks after the acute phase, with decreased physical activity tolerance and activity-induced fatigue as the main features. A positive trend was observed at each follow-up visit as the spectrum of the children's complaints decreased. Furthermore, rapid normalization of laboratory markers and cardiac abnormalities was observed.

Alcoholism and cellular vulnerability in different brain regions.

Alcohol-induced damage causes dysfunction of selected brain regions. Multidisciplinary studies have provided an extensive description of changes observed in neurons and glia following alcohol consumption. In this study the authors have elucidated preferential cellular vulnerability in three different brain regions. Autopsy material of the prefrontal cortex, striatum, and substantia nigra obtained from the brain tissue of alcoholic subjects was used in this study. We found that dendritic tree and astroglial damage is irreversible, while neuronal somata and most axons do not display irreversible changes.

Clinical features of pediatric post-acute COVID-19: a descriptive retrospective follow-up study.

To date, information on COVID-19 long-term post-recovery sequelae in children and adolescents remains scarce. A retrospective descriptive cohort study was performed by collecting data on 92 patients (age ≤ 18 years). All were evaluated during a face-to-face visit following a specially designed post-COVID-19 symptom assessment protocol at the following stage: 1-3 months after COVID-19 onset. Among the 92 children, 45 (49%) were completely free of any COVID-19-related symptoms, while 47 (51%) reported persistence of at least one symptom, in particular tiredness, loss of taste and/or smell and headaches. The most common post-acute COVID-19 clinical features were noted in children aged between 10 and 18 years. A detailed multidisciplinary follow-up of patients with COVID-19 seems relevant, whatever the severity of the symptoms.

Impact of Pediatric COVID-19 on Family Health-Related Quality of Life: A Qualitative Study from Latvia.

Information on family health-related quality of life (FHRQoL) among families of children with the coronavirus disease 2019 (COVID-19) is limited. This qualitative study explores the impact of pediatric COVID-19 on FHRQoL from the parents' perspective. Semi-structured interviews were conducted with parents (n = 20) whose children had tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inductive thematic analysis revealed the following 10 themes that represented parents' perception of FHRQoL while taking care of a child with COVID-19: pediatric COVID-19 as a disease with many unknowns; emotional saturation; internal family relationships in the context of "a new experience"; routine household activities and daily regimen while family is in lockdown; plenty of free time; a wide social support network; social stigma associated with COVID-19; different options for work; savings and debts; challenges with family housing and transport availability. Our results show that parents experience multiple effects of pediatric COVID-19 with regard to FHRQoL.

Comparison of Persistent Symptoms After COVID-19 and Other Non-SARS-CoV-2 Infections in Children.

Introduction: The data on long COVID in children is scarce since children and adolescents are typically less severely affected by acute COVID-19. This study aimed to identify the long-term consequences of SARS-CoV-2 infection in children, and to compare the persistent symptom spectrum between COVID-19 and community-acquired infections of other etiologies. Methods: This was an ambidirectional cohort study conducted at the Children's Clinical University Hospital in Latvia. The study population of pediatric COVID-19 patients and children with other non-SARS-CoV-2-community-acquired infections were invited to participate between July 1, 2020, and April 30, 2021. Results: In total, 236 pediatric COVID-19 patients were enrolled in the study. Additionally, 142 comparison group patients were also enrolled. Median follow-up time from acute symptom onset was 73.5 days (IQR; 43-110 days) in the COVID-19 patient group and 69 days (IQR, 58-84 days) in the comparison group. Most pediatric COVID-19 survivors (70%, N = 152) reported at least one persistent symptom, but more than half of the patients (53%, N = 117) noted two or more long-lasting symptoms. The most commonly reported complaints among COVID-19 patients included persistent fatigue (25.2%), cognitive sequelae, such as irritability (24.3%), and mood changes (23.3%), as well as headaches (16.9%), rhinorrhea (16.1%), coughing (14.4%), and anosmia/dysgeusia (12.3%). In addition, 105 (44.5%) COVID patients had persistent symptoms after the 12-week cut-off point, with irritability (27.6%, N = 29), mood changes (26.7%, N = 28), and fatigue (19.2%, N = 20) being the most commonly reported ones. Differences in symptom spectrum among the various age groups were seen. Logistic regression analysis showed that long-term persistent symptoms as fever, fatigue, rhinorrhea, loss of taste and/or smell, headaches, cognitive sequelae, and nocturnal sweating were significantly associated with the COVID-19 experience when compared with the controls. Conclusions: We found that at the time of interview almost three-quarters of children reported at least one persistent symptom, but the majority of patients (53%) had two or more concurrent symptoms. The comparison group's inclusion in the study allowed us to identify that symptom persistence is more apparent with COVID-19 than any other non-SARS-CoV-2 infection. More research is needed to distinguish the symptoms of long COVID from pandemic-associated complaints. Each persistent symptom is important in terms of child well-being during COVID-19 recovery.

Case Series of Multisystem Inflammatory Syndrome (MIS-C) in Children during the SARS-CoV-2 Pandemic in Latvia.

The total number of COVID-19 positive cases in Latvia has escalated rapidly since October 2020, peaking in late December 2020 and early January 2021. Children generally develop COVID-19 more mildly than adults; however, it can be complicated by multisystem inflammatory syndrome in children (MIS-C). This case study aims were to assess demographic characteristics and the underlying medical conditions, and clinical, investigative and treatment data among 13 MIS-C patients using electronic medical records. All 13 had acute illness or contact with someone who was COVID-19 positive two to six weeks before MIS-C onset. Only five of the 13 were symptomatic during the acute COVID-19 phase. The median age was 8.8 years; 11/13 patients were male, 10/13 had been previously healthy, and all 13 patients tested positive for SARS-CoV-2 by RT-PCR or antibody testing. The most commonly involved organ systems were the gastrointestinal (13/13), hematologic (13/13), cardiovascular (13/13), skin and mucosa (13/13), and respiratory (12/13) ones. The median hospital stay was 13 (interquartile range, 11 to 18) days; 7/13 patients received intensive care, 6/13 oxygen support, and 5/13 received inotropic support. No deaths occurred. During the current pandemic, every child with a fever should have a clearly defined epidemiological history of COVID-19, a careful clinical assessment of possible multiple organ-system involvement, with a special focus on children with severe abdominal pain and/or skin and mucocutaneous lesions.

Case Series of Variable Acute Appendicitis in Children with SARS-CoV-2 Infection.

This case series study consists of six children, aged 5-16 years, admitted to a centralized tertiary paediatric hospital serving a population of 1.9 million with acute appendicitis in the setting of SARS-CoV-2 infection. From the beginning of the pandemic in March 2020 until August 2021, 121 COVID-19-positive children were admitted to the hospital. A total of 49 (40.5%) of these patients presented with gastrointestinal symptoms, of which six were diagnosed with acute appendicitis. Five underwent an appendectomy, while one was treated conservatively. To date, it has been reported that appendicitis may have a plausible association with SARS-CoV-2 infection in children. With COVID-19 cases rising, every medical specialist, including all paediatric surgeons, must be ready to treat common acute diseases with SARS-CoV-2 infection as a comorbidity. Providers should consider testing for this infection in paediatric patients with severe gastrointestinal symptoms. Non-surgical treatment of acute appendicitis in children may gain new importance during and after the COVID-19 pandemic. Further studies are needed to prove the link of causality between COVID-19 and acute appendicitis in children.

Persistent clinical features in paediatric patients after SARS-CoV-2 virological recovery: a retrospective population-based cohort study from a single centre in Latvia.

The COVID-19 related state of emergency in Latvia was declared on 12 March 2020. Consequently, Children's Clinical University Hospital in Riga, Latvia, established a postacute outpatient service for individuals after recovery from COVID-19. Although information regarding the epidemiology and clinical features of COVID-19 in children has accumulated, relevant reports about persistent symptoms after recovery are lacking. We aimed to determine data on COVID-19 persistent symptoms after recovery in children in Latvia. Persistent symptoms have been reported in 9 out of 30 children.

Rotavirus-associated seizures and reversible corpus callosum lesion.

Rotavirus is a non-enveloped double-stranded RNA virus that causes severe gastroenteritis in children, but complications are rarely reported. Some reports have shown that rotavirus can induce diverse complications of the central nervous system, such as seizures, encephalopathy with a reversible splenial lesion, encephalitis, cerebral white matter abnormalities, and cerebellitis. Here, we present a 2-year-old patient with seizures, who had an isolated splenial lesion in the corpus callosum on neuroimaging, and the rotavirus antigen detected in faeces.

Evaluation of the presence of MMP-2, TIMP-2, BMP2/4, and TGFß3 in the facial tissue of children with cleft lip and palate.

Cleft lip and palate (CLP) is the most common defect affecting the face. The treatment consists of surgical reconstruction of the anatomical structures of the cleft. Part of the surgical treatment is reconstruction of the alveolar bone by means of autogenic bone grafting (osteoplasty). This study aimed to evaluate the levels of expression of extracellular matrix remodeling factors in the facial tissue of children with a complete unilateral (CU) and a complete bilateral (CB) CLP to assess whether the wound healing process is adequate. Twenty-two CLP patients were enrolled in this study. Tissue samples were collected during alveolar osteoplasty for unilateral (n = 12) or bilateral (n = 10) cleft palate, (age range from 6 years 8 months to 12 years 2 months). Control material was obtained in the case of tooth extraction (age range from 6 years 9 months to 14 years 5 months). Immunohistochemistry was used to assess the levels of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), bone morphogenetic proteins 2 and 4 (BMP2/4), and transforming growth factor ß3 (TGFß3). Numbers of positively stained cells were graded semi-quantitatively. Data were analysed using the Kraskel-Wallis rank test and the Bonferroni correction. The total number of MMP2-positive cells was significantly lower in the CBCLP and in the control group than in the CUCLP (p < 0.001 after the Bonferroni correction). The total number of TIMP2-positive cells was significantly higher in the CUCLP than in the CBCLP and in the control group (p < 0.001; p < 0.003 after the Bonferroni correction). The overall number of BMP2/4, TGFß3-positive cells was significantly higher in the CUCLP than in the CBCLP and in the control group (p < 0.001 after the Bonferroni correction). The decrease of the relative amount of statistically significant BMP2/4, TGFß3, MMP-2, TIMP-2 containing bone cells in CBCLP patients identifies affected alveolar bone regeneration and remodeling process.

Apoptosis and MMP-2, TIMP-2 expression in cleft lip and palate.

Aim of our study was complex detection of appearance and distribution of specific signalling proteins and apoptosis in facial tissue of children with complete bilateral cleft lip and palate (CBCLP). MATERIALS AND METHODS. Nineteen CBCLP patients and 11 unaffected subjects were involved in this study. All the tissue samples were proceeded for detection of matrix metalloproteinase-2 (MMP-2), tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and apoptosis. The intensity of immunostaining was graded semi-quantitatively. Results of the terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) method were obtained by counting apoptosis positive cells in five unintentionally chosen fields of vision. Groups were compared using the Mann-Whitney test. RESULTS. TUNEL-positive oral epithelial cells were significantly increased in the control group when compared with the CBCLP group. Connective tissue cells have a statistically significant lower expression of TIMP-2 in the control group compared to the CBCLP group. CONCLUSIONS. TIMP-2 positive connective tissue cells increasingly found in oral mucosa lamina propria proves the decrease of local apoptosis in CLP patients. Prominent expression of MMP-2 in cleft affected soft tissue indicates a possible increase of tissue remodelling.

Proliferative potential in benign mixed salivary gland tumors and its value in primary and recurrent neoplasms.

OBJECTIVE. Mixed salivary gland tumors are characterized by a marked diversity in the cell proliferation. It course in the stromal component, and, especially in recurrent neoplasms, is not completely understood. This study evaluated cell proliferative potential, its value and the clinical course of primary and recurrent salivary gland pleomorphic adenomas (PA). MATERIALS AND METHODS. 322 benign salivary gland tumors were used in this study. The cell proliferation was estimated by Ki-67 expression levels. RESULTS. Ki-67 immunoreactivity showed a wide range of spectra; in the epithelial and stromal type of PA the cell proliferation had the value from 0.07±0.03 (95% CI 0.01-0.14) to 4.81±0.60 (95% CI 3.61-6.02) and from 0 to 0.79±0.11 (95% CI 0.57-1.00), respectively. The Ki-67 value was higher in recurrent tumors compared with primary, and the mean number of Ki-67-positive cells per visual microscopic field constituted 2.14±1.60 (95% CI 1.47-2.47) comparing with 1.43 (95% CI 0.97-1.55) revealed in primary tumors. CONCLUSION. Cell proliferation values correlate with a recurrence of neoplasm, and elevation of proliferation potential in the stromal component of recurrent PA is indicative of clinical course change for the worse.

IRF6, RYK, and PAX9 expression in facial tissue of children with cleft palate / Expresión de IRF6, RYK y PAX9 en el tejido facial de niños con paladar fisurado

Cleft lip and palate (CLP) is a congenital anomaly characterized by the inappropriate fusion of the upper lip, alveolus, and secondary palate. This study investigated whether expression of interferon regulatory fac tor 6 (IRF6), receptor-like tyrosine kinase (RYK), and paired-box 9 (PAX9), which are essential for the normal development and morphogenesis of craniofacial structures, is dysregulated in children with CLP. Oral mucosa tissue samples were obtained from patients with complete bilateral (CB) CLP (n= 19) during corrective plastic surgery and unaffected control subjects (n= 7). IRF6, RYK, and PAX9 expression was assessed by immunohistochemistry, and data were analyzed with the Mann-Whitney test. In patients, IRF6 immunoreactivity in the connective tissue was moderate to high, but the overall number of IRF6-positive oral epithelial cells was lower than that in controls (z= -3.41; P= 0.01). RYK expression was observed only sporadically in the oral epithelium of 4 patients, in contrast to the control group (z= -3.75; P< 0.001). PAX9-positive epithelial cells were present in low to moderate numbers in patients with CBCLP, while an abundance of these cells was observed in the basal layer of the oral epithelium in controls (z= -3.60; P<0.001). IRF6 is the main connective tissue regulatory factor in CBCLP, and its low level of expression in the oral epithelium suggests a reduced potential for epitheliocyte differentiation, while low PAX9 and RYK expression may explain the decreased cell migration and cleft remodeling in CBCLP.

La fisura labial y palatina (FLP) son anomalías congénitas caracterizadas por la fusión inadecuada del labio superior, alvéolo y paladar secundario. En este estudio se investigó si en niños con FLP hay una desregulación de la expresión del factor regulador de interferón 6 (IRF6), del receptor de la tirosina quinasa (RYK), y del factor de transcripción PAX9, que son esenciales para el desarrollo normal y la morfogénesis de las estructuras craneofaciales. Se obtuvieron muestras de la mucosa oral de pacientes con FLP completa bilateral (CB) (n= 19), tomadas durante la realización de cirugía plástica correctiva, y de sujetos de control no afectados (n= 7). Se evaluó la expresión de IRF6, RYK y PAX9 por inmunohistoquímica, y los datos se analizaron con la prueba de Mann-Whitney. En los pacientes, la inmunoreactividad de IRF6 en el tejido conectivo fue de moderada a alta, pero el número total de células epiteliales orales positivas para IRF6 fue menor que en los controles (z= -3,41; P= 0,01). La expresión de RYK se observó sólo esporádicamente en el epitelio oral de 4 pacientes, en contraste con el grupo control (z= -3,75; P<0.001). Células epiteliales positivas para PAX9 estaban presentes en números bajos a moderados en pacientes con FLP completa bilateral, mientras que se observó una abundante cantidad de estas células en la capa basal del epitelio oral en los controles (z= -3,60; P<0,001). IRF6 es el principal factor regulador del tejido conectivo con FLP completa bilateral, y su bajo nivel de expresión en el epitelio oral sugiere un potencial reducido para la diferenciación del epitelio, mientras que la expresión baja de PAX9 y RYK pueden explicar la disminución de la migración celular y la remodelación de la fisura con FLP completa bilateral.