Age at onset of alcohol consumption and its association with alcohol misuse in adulthood.

OBJECTIVE: This study aimed to explore the association between early age onset of alcohol consumption and alcohol misuse in adulthood. METHODS: The study sample consisted of 16 829 individuals' (8349 males, 8435 females) survey responses obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2016 through 2019. Alcohol dependence was measured using the AUDIT-C (Alcohol Use Disorder Identification Test-Consumption), and the ages at which alcohol consumption began were grouped into four categories: under 16, 16 to 18, 19 to 23, and over 24. Multiple logistic regression was used to examine the association between current alcohol misuse and age at onset of alcohol consumption. RESULTS: Compared to individuals who started drinking alcohol after the age of 24, those who began drinking alcohol before the age of 16 were more likely to score 8 or more on AUDIT-C questions (under 16: males, odds ratio [OR] 2.50, confidence interval [CI] 1.97-3.17; females, OR: 1.66, CI: 1.18-2.33). Similar to the main analysis, the earlier the onset of alcohol assumption starts, the more likely one is to develop alcohol misuse in adulthood according to subgroup analysis stratified by independent variables in both gender. CONCLUSION: The lower the age at the onset of alcohol consumption, the higher the likelihood of alcohol misuse in adulthood. While both males and females showed the same trend in response to the AUDIT-C questions, males tended to have a stronger association between early onset alcohol consumption and alcohol misuse.

New-onset functional seizures during the COVID-19 pandemic.

OBJECTIVE: We investigated whether the COVID-19 pandemic has influenced the characteristics of functional seizures (FS) at the onset of seizures. METHODS: This was a retrospective study of all patients with new-onset FS, who were admitted at the epilepsy monitoring unit at Shiraz University of Medical Sciences, Shiraz, Iran, during two time periods: the onset of FS and also the diagnosis of FS in 2017-2019 (pre-COVID era) and the onset of FS and also the diagnosis of FS in 2020-2021 (COVID era). RESULTS: Forty-five patients were studied (32 patients from the pre-COVID era and 13 patients from the COVID era). Patients who developed FS during the pandemic more likely had comorbid epilepsy compared with the patients who presented with FS before the pandemic [30.1% vs. 9.4%; Odds ratio (OR): 81.2]. Furthermore, those who developed FS during the pandemic more likely were employed compared with the patients who presented with FS before the pandemic (46.2% vs. 12.5%; OR: 16.2). A family history of seizures was associated with the FS timing as a trend (OR: 8.4); those who developed FS during the pandemic more likely had a family history of seizures compared with the patients who presented with FS before the pandemic (53.8% vs. 18.8%). CONCLUSION: This study showed that patients who developed FS during the COVID-19 pandemic had significant underlying differences (i.e., employment status, comorbid epilepsy, and a family history of seizures) compared with those who presented with FS before the pandemic.

Clinical and Radiological Characteristics of Children and Adults With First-Attack Myelin Oligodendrocyte Glycoprotein Antibody Disease and Analysis of Risk Factors for Predicting the Severity at Disease Onset in Central China.

Objective: To analyze and compare different clinical, laboratory, and magnetic resonance imaging characteristics between pediatric and adult patients with first-attack myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and to explore predictive factors for severity at disease onset. Methods: Patients diagnosed with MOGAD at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2021 were enrolled in this retrospective study. Age at disease onset, sex, comorbidities, laboratory tests, magnetic resonance imaging (MRI) characteristics, and Expanded Disability Status Scale (EDSS) scores were collected and analyzed. The association between risk factors and initial EDSS scores at disease onset was analyzed using logistic regression models and Spearman correlation analyses. A receiver-operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of the uric acid and homocysteine (Hcy) levels for the severity of neurological dysfunction at the onset of MOGAD. Results: Sixty-seven patients (female, n=34; male, n=33) with first-attack MOGAD were included in this study. The mean age at onset was 26.43 ± 18.22 years (range: 3-79 years). Among patients <18 years of age, the most common presenting symptoms were loss of vision (36.0%), and nausea and vomiting (24.0%), and the most common disease spectrum was acute disseminated encephalomyelitis (ADEM) (40.0%). Among patients aged ≥18 years, the most common presenting symptoms were loss of vision (35.7%), paresthesia (33.3%), and paralysis (26.2%), and the most common disease spectrum was optic neuritis (35.7%). The most common lesions were cortical gray matter/paracortical white matter lesions in both pediatric and adult patients. Uric acid [odds ratio (OR)=1.014; 95% confidence interval (CI)=1.006-1.022; P=0.000] and serum Hcy (OR=1.125; 95% CI=1.017-1.246; P=0.023) levels were significantly associated with the severity of neurological dysfunction at disease onset. Uric acid levels (r=0.2583; P=0.035) and Hcy levels (r=0.3971; P=0.0009) were positively correlated with initial EDSS scores. The areas under the ROC curve were 0.7775 (95% CI= 0.6617‒0.8933; P<0.001) and 0.6767 (95% CI=0.5433‒0.8102, P=0.014) for uric acid and Hcy levels, respectively. Conclusion: The clinical phenotype of MOGAD varies in patients of different ages. The most common disease spectrum was ADEM in patients aged<18 years, while optic neuritis was commonly found in patients aged ≥18 years. The uric acid and Hcy levels are risk factors for the severity of neurological dysfunction at disease onset in patients with first-attack MOGAD.

Therapeutic Underuse and Delay in Hepatocellular Carcinoma: Prevalence, Associated Factors, and Clinical Impact.

Prognosis of hepatocellular carcinoma (HCC) could be affected by lack of or delayed therapy. We aimed to characterize the prevalence, correlates, and clinical impact of therapeutic underuse and delay in patients with HCC. Patients with HCC diagnosed between 2010 and 2017 were analyzed from the United States National Cancer Database. Logistic regression analysis identified factors associated with no and delayed (>90 days after diagnosis) HCC treatment. Cox proportional hazards regression with landmark analysis assessed the association between therapeutic delay and overall survival (OS), accounting for immortal time bias. Of 116,299 patients with HCC, 24.2% received no treatment and 18.4% of treated patients had delayed treatment. Older age, Black, Hispanic, lower socioeconomic status, earlier year of diagnosis, treatment at nonacademic centers, Northeast region, increased medical comorbidity, worse liver dysfunction, and higher tumor burden were associated with no treatment. Among treated patients, younger age, Hispanic, Black, treatment at academic centers, West region, earlier tumor stage, and receipt of noncurative treatment were associated with treatment delays. In multivariable Cox regression with a landmark of 150 days, patients with and without treatment delays had similar OS (adjusted hazard ratio [aHR], 1.01; 95% confidence interval [CI], 0.98-1.04) with a median survival of 33.7 vs. 32.1 months, respectively. However, therapeutic delay was associated with worse OS in patients who had tumor, nodes, and metastases (TNM) stage 1 (aHR, 1.06; 95% CI, 1.01-1.11) or received curative treatment (aHR, 1.12; 95% CI, 1.05-1.18). Conclusion: One-fourth of patients with HCC receive no therapy and one-fifth of treated patients experience treatment delays. Both were associated with demographic, socioeconomic, and clinical characteristics of patients as well as facility type and region. The association between therapeutic delay and survival was stage and treatment dependent.

Effect of COVID-19 on Kawasaki Disease: Decrease Age of Onset and Increase Skin Manifestation.

BACKGROUND: Kawasaki Disease (KD) is the most common childhood vasculitis and cause of acquired heart disease for no apparent reason. There is some evidence indicating infectious agents as possible triggers for KD. During the COVID-19 pandemic, vasculitis has been a presentation of COVID-19 in children. We performed this study to assess the association between KD and COVID-19. We evaluated KD hospitalized children during February to September 2020 for COVID-19 (group one) and compared their demographic, clinical, laboratory, and echocardiographic findings with KD patients from the same period time in 2019 (group two). We also compared the same data in COVID-19 positive and COVID-19 negative KD patients in 2020 pandemic period in Shiraz Namazi referral hospital at southwest of Iran. RESULTS: Thirty-two patients in group one compared with 44 patients in group two. Sixty-eight percent of group one KD patients were positive for COVID-19 during the pandemic period. KD Age of onset in the group one was lower than group two (4.38 years VS 5.5 years, P-value = 0.044). There was no difference in the demographic, clinical, laboratory, and echocardiographic features of the patients during and before the COVID-19 pandemic (p-value > 0.05). Moreover, Comparing COVID-19 positive and negative the incidence of rash was higher within COVID-19 positive cases (p < 0.05), and coronary artery abnormalities were more prevalent in COVID-19 negative cases (p < 0.05). CONCLUSION: Admission rate of KD was almost similar during the COVID-19 pandemic but 68% of KD admitted patient were COVID-19 positive. Age of onset for KD during the COVID-19 pandemic was lower and skin manifestation was higher than the same period time in last year.

A Review on the Role of Stem Cells against SARS-CoV-2 in Children and Pregnant Women.

Since the COVID-19 outbreak was acknowledged by the WHO on 30 January 2020, much research has been conducted to unveil various features of the responsible SARS-CoV-2 virus. Different rates of contagion in adults, children, and pregnant women may guide us to understand the underlying infection conditions of COVID-19. In this study, we first provide a review of recent reports of COVID-19 clinical outcomes in children and pregnant women. We then suggest a mechanism that explains the curious case of COVID-19 in children/pregnant women. The unique stem cell molecular signature, as well as the very low expression of angiotensin-converting enzyme 2 and the lower ACE/ACE2 ratio in stem cells of children/pregnant women compared to adults might be the cause of milder symptoms of COVID-19 in them. This study provides the main molecular keys on how stem cells can function properly and exert their immunomodulatory and regenerative effects in COVID-19-infected children/pregnant women, while failing to replicate their role in adults. This can lay the groundwork for both predicting the pattern of spread and severity of the symptoms in a population and designing novel stem cell-based treatment and prevention strategies for COVID-19.

The effect of the COVID-19 pandemic on metabolic control in children with type 1 diabetes: a single-center experience.

OBJECTIVES: Coronavirus disease 2019 has caused a major epidemic worldwide, and lockdowns became necessary in all countries to prevent its spread. This study aimed to evaluate the effects of staying-at-home practices on the metabolic control of children and adolescents with type 1 diabetes during the pandemic period. MATERIALS AND METHODS: Eighty-nine patients younger than 18 years old who were diagnosed with type 1 diabetes at least one year before the declaration of the pandemic were included in the study. The last visit data of the patients before and after the declaration of the pandemic, and the frequency of presentation of diabetes-related emergencies from one year after diagnosis of type 1 diabetes to the declaration of the pandemic, and from the declaration of the pandemic to the last visit after the pandemic declaration were compared. RESULTS: The total number of patients was 89, and 48 (53.9%) were boys. The mean (± standard deviation [SD]) age at diagnosis was 8.4 ± 3.7 years (boys 7.9 ± 3.6 years; girls 8.9 ± 3.9 years). There was no statistically significant difference when the SD values of the anthropometric measurements, and the glycosylated hemoglobin (HbA1c) and lipid profile tests were compared. However, the frequency of admission to the emergency service related to diabetes was significantly different. CONCLUSIONS: Although the pandemic did not significantly affect the metabolic and glycemic controls of the children with type 1 diabetes included in this study, an increase in the frequency of diabetes-related emergency admissions was noted.

The Holocaust Is a Significant and Independent Risk Factor of Late-Onset Cancers: A Systematic Review of the Literature and Original Data on Jewish Israeli, Jewish Non-Israeli and Non-Jewish Non-Israeli Survivors.

BACKGROUND/AIM: Seventy-six years after Auschwitz Liberation, the Holocaust keeps on persecuting its surviving victims. As witnessed by the psychiatric and medical literature in the last decades, in fact, the Holocaust survivors (HS) appear to suffer from several Shoah-related late-onset diseases impacting their survival, such as internal illnesses and post-traumatic stress disorder (PTSD). Cancer represents a further severe pathology which seems to be connected with the Holocaust experience. Our aim was to review the existing knowledge of Holocaust-related cancer in HS in order to assess its real incidence and clinicoprognostic significance. MATERIALS AND METHODS: We systematically reviewed the literature dealing with Israeli Jewish and non-Jewish non-Israeli HS developing cancer. We also reviewed and analyzed the cancer data of noted Jewish HS not resident or having resided in Israel available as public information. RESULTS: We found 16 and 15 studies on Israeli Jews and non-Jewish non-Israeli survivors, respectively. A statistically significant association between the Holocaust and development of late-onset cancer in HS was seen in most studies with cancer adversely impacting the survival. We also selected 330 noted Jewish non-Israeli HS: genocide-related late-onset cancer resulted to be a significant and independent risk factor of poor prognosis (p<0.0001) imparting shorter survival in affected versus non-cancer subjects (57 versus 64 years, respectively, p=0.0001). CONCLUSION: Although 76 years have passed, our review shows how the Holocaust keeps on burdening its survivors. Moreover, we offered the first analysis of Jewish HS not resident or having resided in Israel in terms of genocide-related late-onset diseases focusing on cancer. Further studies on Jewish non-Israeli HS are needed in order to corroborate our findings on late-onset cancer occurring in this targeted population.

Differentiating multisystem inflammatory syndrome in children: a single-centre retrospective cohort study.

OBJECTIVE: Features of multisystem inflammatory syndrome in children (MIS-C) overlap with other febrile illnesses, hindering prompt and accurate diagnosis. The objectives of this study were to identify clinical and laboratory findings that distinguished MIS-C from febrile illnesses in which MIS-C was considered but ultimately excluded, and to examine the diseases that most often mimicked MIS-C in a tertiary medical centre. STUDY DESIGN: We identified all children hospitalised with fever who were evaluated for MIS-C at our centre and compared clinical signs and symptoms, SARS-CoV-2 status and laboratory studies between those with and without MIS-C. Multivariable logistic LASSO (least absolute shrinkage and selection operator) regression was used to identify the most discriminative presenting features of MIS-C. RESULTS: We identified 50 confirmed MIS-C cases (MIS-C+) and 68 children evaluated for, but ultimately not diagnosed with, MIS-C (MIS-C-). In univariable analysis, conjunctivitis, abdominal pain, fatigue, hypoxaemia, tachypnoea and hypotension at presentation were significantly more common among MIS-C+ patients. MIS-C+ and MIS-C- patients had similar elevations in C-reactive protein (CRP), but were differentiated by thrombocytopenia, lymphopenia, and elevated ferritin, neutrophil/lymphocyte ratio, BNP and troponin. In multivariable analysis, predictors of MIS-C included age, neutrophil/lymphocyte ratio, platelets, conjunctivitis, oral mucosa changes, abdominal pain and hypotension. CONCLUSIONS: Among hospitalised children undergoing evaluation for MIS-C, children with MIS-C were older, more likely to present with conjunctivitis, oral mucosa changes, abdominal pain and hypotension, and had higher neutrophil/lymphocyte ratios and lower platelet counts. These data may be helpful for discrimination of MIS-C from other febrile illnesses, including bacterial lymphadenitis and acute viral infection, with overlapping features.

Humoral signatures of protective and pathological SARS-CoV-2 infection in children.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte-activating SARS-CoV-2 IgG antibodies, distinguishable from acute disease in children but with antibody levels similar to those in convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that might underlie differential disease severity as well as unexpected complications in children infected with SARS-CoV-2.

SARS-CoV-2 Among Infants <90 Days of Age Admitted for Serious Bacterial Infection Evaluation.

OBJECTIVES: To determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants hospitalized for a serious bacterial infection (SBI) evaluation and clinically characterize young infants with SARS-CoV-2 infection. METHODS: A retrospective chart review was conducted on infants <90 days of age hospitalized for an SBI evaluation. The study was conducted at 4 inpatient facilities in New York City from March 15, 2020, to December 15, 2020. RESULTS: We identified 148 SBI evaluation infants who met inclusion criteria. A total of 22 infants (15%) tested positive for SARS-CoV-2 by nasopharyngeal reverse transcription polymerase chain reaction; 31% of infants admitted during periods of high community SARS-CoV-2 circulation tested positive for SARS-CoV-2, compared with 3% when community SARS-CoV-2 circulation was low (P < .001). The mean age of infants with SARS-CoV-2 was higher than that of SARS-CoV-2-negative infants (33 [SD: 17] days vs 23 [SD: 23] days, respectively; P = .03), although no age difference was observed when analysis was limited only to febrile infants. An isolated fever was the most common presentation of SARS-CoV-2 (n = 13; 59%). Admitted infants with SARS-CoV-2 were less likely to have positive urine culture results (n = 1 [5%] versus n = 25 [20%], respectively; P = .002), positive cerebrospinal culture results (n = 0 [0%] versus n = 5 [4%], respectively; P = .02), or be admitted to intensive care (n = 2 [9%] versus n = 47 [37%]; P < .001), compared with infants without SARS-CoV-2. CONCLUSIONS: SARS-CoV-2 was common among young infants hospitalized for an SBI evaluation during periods of high but not low community SARS-CoV-2 circulation in New York City, although most infants did not require intensive care admission.

The selection of indicators from initial blood routine test results to improve the accuracy of early prediction of COVID-19 severity.

The global pandemic of COVID-19 poses a huge threat to the health and lives of people all over the world, and brings unprecedented pressure to the medical system. We need to establish a practical method to improve the efficiency of treatment and optimize the allocation of medical resources. Due to the influx of a large number of patients into the hospital and the running of medical resources, blood routine test became the only possible check while COVID-19 patients first go to a fever clinic in a community hospital. This study aims to establish an efficient method to identify key indicators from initial blood routine test results for COVID-19 severity prediction. We determined that age is a key indicator for severity predicting of COVID-19, with an accuracy of 0.77 and an AUC of 0.92. In order to improve the accuracy of prediction, we proposed a Multi Criteria Decision Making (MCDM) algorithm, which combines the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) and Naïve Bayes (NB) classifier, to further select effective indicators from patients' initial blood test results. The MCDM algorithm selected 3 dominant feature subsets: {Age, WBC, LYMC, NEUT} with a selection rate of 44%, {Age, NEUT, LYMC} with a selection rate of 38%, and {Age, WBC, LYMC} with a selection rate of 9%. Using these feature subsets, the optimized prediction model could achieve an accuracy of 0.82 and an AUC of 0.93. These results indicated that Age, WBC, LYMC, NEUT were the key factors for COVID-19 severity prediction. Using age and the indicators selected by the MCDM algorithm from initial blood routine test results can effectively predict the severity of COVID-19. Our research could not only help medical workers identify patients with severe COVID-19 at an early stage, but also help doctors understand the pathogenesis of COVID-19 through key indicators.

Cerebrospinal fluid findings in patients with psychotic symptoms-a retrospective analysis.

In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are based on symptomatic descriptions since no unambiguous biomarkers are known to date. However, when underlying causes of psychotic symptoms, like inflammation, ischemia, or tumor affecting the neural tissue can be identified, a different classification is used ("psychotic disorder with delusions due to known physiological condition" (ICD-10: F06.2) or psychosis caused by medical factors (DSM5)). While CSF analysis still is considered optional in current diagnostic guidelines for psychotic disorders, CSF biomarkers could help to identify known physiological conditions. In this retrospective, partly descriptive analysis of 144 patients with psychotic symptoms and available CSF data, we analyzed CSF examinations' significance to differentiate patients with specific etiological factors (F06.2) from patients with schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F2). In 40.3% of all patients, at least one CSF parameter was out of the reference range. Abnormal CSF-findings were found significantly more often in patients diagnosed with F06.2 (88.2%) as compared to patients diagnosed with F2 (23.8%, p < 0.00001). A total of 17 cases were identified as probably caused by specific etiological factors (F06.2), of which ten cases fulfilled the criteria for a probable autoimmune psychosis linked to the following autoantibodies: amphiphysin, CASPR2, CV2, LGl1, NMDA, zic4, and titin. Two cases presented with anti-thyroid tissue autoantibodies. In four cases, further probable causal factors were identified: COVID-19, a frontal intracranial tumor, multiple sclerosis (n = 2), and neurosyphilis. Twenty-one cases remained with "no reliable diagnostic classification". Age at onset of psychotic symptoms differed between patients diagnosed with F2 and F06.2 (p = 0.014), with the latter group being older (median: 44 vs. 28 years). Various CSF parameters were analyzed in an exploratory analysis, identifying pleocytosis and oligoclonal bands (OCBs) as discriminators (F06.2 vs. F2) with a high specificity of > 96% each. No group differences were found for gender, characteristics of psychotic symptoms, substance dependency, or family history. This study emphasizes the great importance of a detailed diagnostic workup in diagnosing psychotic disorders, including CSF analysis, to detect possible underlying pathologies and improve treatment decisions.

The clinical spectrum of COVID-19-associated cutaneous manifestations: An Italian multicenter study of 200 adult patients.

BACKGROUND: COVID-19 is associated with a wide range of skin manifestations. OBJECTIVE: To describe the clinical characteristics of COVID-19-associated skin manifestations and explore the relationships among the 6 main cutaneous phenotypes and systemic findings. METHODS: Twenty-one Italian Dermatology Units were asked to collect the demographic, clinical, and histopathologic data of 200 patients with COVID-19-associated skin manifestations. The severity of COVID-19 was classified as asymptomatic, mild, moderate, or severe. RESULTS: A chilblain-like acral pattern was significantly associated with a younger age (P < .0001) and, after adjusting for age, significantly associated with less severe COVID-19 (P = .0009). However, the median duration of chilblain-like lesions was significantly longer than that of the other cutaneous manifestations taken together (P < .0001). Patients with moderate/severe COVID-19 were more represented than those with asymptomatic/mild COVID-19 among the patients with cutaneous manifestations other than chilblain-like lesions, but only the confluent erythematous/maculo-papular/morbilliform phenotype was significantly associated with more severe COVID-19 (P = .015), and this significance disappeared after adjustment for age. LIMITATIONS: Laboratory confirmation of COVID-19 was not possible in all cases. CONCLUSIONS: After adjustment for age, there was no clear-cut spectrum of COVID-19 severity in patients with COVID-19-related skin manifestations, although chilblain-like acral lesions were more frequent in younger patients with asymptomatic/pauci-symptomatic COVID-19.