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Since the reintroduction of African swine fever virus (ASFV) in Europe in 2007 and its subsequent spread to Asia, wild boar has played a crucial role in maintaining and disseminating the virus. There are significant gaps in the knowledge regarding infection dynamics and disease pathogenesis in domestic pigs and wild boar, particularly at the early infection stage. We aimed to compare domestic pigs and wild boar infected intranasally to mimic natural infection with one of the original highly virulent genotype II ASFV isolates (Armenia 2007). The study involved euthanising three domestic pigs and three wild boar on days 1, 2, 3, and 5 post-infection, while four domestic pigs and four wild boar were monitored until they reached a humane endpoint. The parameters assessed included clinical signs, macroscopic lesions, viremia levels, tissue viral load, and virus shedding in nasal and rectal swabs from day 1 post-infection. Compared with domestic pigs, wild boar were more susceptible to ASFV, with a shorter incubation period and earlier onset of clinical signs. While wild boar reached a humane endpoint earlier than domestic pigs did, the macroscopic lesions were comparatively less severe. In addition, wild boar had earlier viremia, and the virus was also detected earlier in tissues. The medial retropharyngeal lymph nodes were identified as key portals for ASFV infection in both subspecies. No viral genome was detected in nasal or rectal swabs until shortly before reaching the humane endpoint in both domestic pigs and wild boar, suggesting limited virus shedding in acute infections. [ABSTRACT FROM AUTHOR]

Abstract Since the reintroduction of African swine fever virus (ASFV) in Europe in 2007 and its subsequent spread to Asia, wild boar has played a crucial role in maintaining and disseminating the virus. There are significant gaps in the knowledge regarding infection dynamics and disease pathogenesis in domestic pigs and wild boar, particularly at the early infection stage. We aimed to compare domestic pigs and wild boar infected intranasally to mimic natural infection with one of the original highly virulent genotype II ASFV isolates (Armenia 2007). The study involved euthanising three domestic pigs and three wild boar on days 1, 2, 3, and 5 post-infection, while four domestic pigs and four wild boar were monitored until they reached a humane endpoint. The parameters assessed included clinical signs, macroscopic lesions, viremia levels, tissue viral load, and virus shedding in nasal and rectal swabs from day 1 post-infection. Compared with domestic pigs, wild boar were more susceptible to ASFV, with a shorter incubation period and earlier onset of clinical signs. While wild boar reached a humane endpoint earlier than domestic pigs did, the macroscopic lesions were comparatively less severe. In addition, wild boar had earlier viremia, and the virus was also detected earlier in tissues. The medial retropharyngeal lymph nodes were identified as key portals for ASFV infection in both subspecies. No viral genome was detected in nasal or rectal swabs until shortly before reaching the humane endpoint in both domestic pigs and wild boar, suggesting limited virus shedding in acute infections.

Background: The complete blood count (CBC) profile has been found extremely useful in monitoring the growth of SARS-CoV-2 infection; however, predictive CBC parameters that could be used in the management of the disease may vary in different populations. Methods: This study comparatively analyzed the CBC profile of SARS-CoV-2 patients (N = 75; confirmed positive by real-time polymerase chain reaction [PCR]) and healthy individuals (confirmed negative by real-time PCR) from Kashmir (north India). Results: Compared with healthy individuals, most of the CBC parameters (hemoglobin levels [13.43 vs 10.9 g/dL; P = 0.0001], lymphocytes [16.04% vs 30.8%; P = 0.00001], monocytes [5.53% vs 7.53%; P = 0.009], and platelet count [150 vs 186 ×103 µL; P = 0.037]) were significantly low in SARS-CoV-2 infected patients, while neutrophilia was more common in infected patients (76.77% vs 59.26%). Among derived parameters, the neutrophil-to-lymphocyte ratio (NLR; 7.31 vs 2.04; P = 0.001) and derived NLR (d-NLR; 4.43 vs 1.5; P = 0.0002) were significantly high in SARS-CoV-2 patients. Further correlation analysis revealed a significant association of neutrophilia with the severity of the disease in SARS-CoV-2 infected patients. Moreover, receiver operating characteristic (ROC) analysis of derived CBC parameters (NLR, d-NLR, and platelet‐to-lymphocyte ratio [PLR] with disease severity and disease outcome) revealed d-NLR as better predictive marker of disease severity (area under the curve [AUC] = 0.658) and disease outcome (AUC = 0.766) compared to PLR with disease severity (AUC = 0.645) and disease outcome (AUC = 0.693). Conclusion: We therefore conclude, of the CBC parameters neutrophilia as the marker of disease severity and among derived parameters, d-NLR as an early predictive biomarker of both disease severity and poor disease outcome in SARS-CoV-2 patients.

Introduction: The hemogram and hemogram-derivative ratios (HDRs) are becoming markers of the severity and mortality of COVID-19. We evaluated the hemograms and serial weekly HDRs [neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), neutrophil-platelet ratio (NPR) and systemic immune-inflammatory index (SII)] in the survivors and non-survivors of COVID-19. Methods: We retrospectively reviewed the medical notes and serial hemograms of real-time reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 adults hospitalized from April 2020 to March 2021 from the time of diagnosis to the 3rd week of diagnosis. Results: Of the 320 adults, 257 (80.3%) were survivors and had a lower mean age than the non-survivors (57.73 vs. 64.65 years, p < 0.001). At diagnosis, the non-survivors had lower hematocrit (p = 0.021), and lymphocyte (p = 0.002) and basophil (p = 0.049) counts and the hematocrit showed a p-value (Is this what you meant???) of 0.021); higher NLR (p < 0.001), PLR (p = 0.047), NPR (p = 0.022) and SII (p = 0.022). Using general linear models, the survivors and non-survivors showed significant variations with weekly lymphocyte count (p < 0.001), neutrophil count (p = 0.005), NLR (p = 0.009), MLR (p = 0.010) and PLR (p = 0.035). All HDRs remained higher in the non-survivors in the 2nd week and 3rd week of diagnosis and the HDRs were higher in the intubated patients than in the non-intubated patients. The NLR and SII were more efficient predictors of mortality in COVID-19 patients. Conclusions: This study shows that serial lymphocyte and neutrophil counts, NLR, PLR, MLR, NPR and SII could serve as good and easily accessible markers of severity and predictors of outcomes in COVID-19 patients and should be used for the monitoring of treatment response.

Objective To investigate the correlation between serum protein 16（CC16), soluble advanced glycation end product receptor (sRAGE) and the disease outcome in patients with acute respiratory distress syndrome（ARDS) and their predictive value. Methods A total of 127 ARDS patients admitted to the Second People′s Hospital of lingbao city from January 2021 to January 2023 were selected as the research objects, and the patients were divided into the mild group（39 cases), the moderate group（52 cases) and the severe group（36 cases) according to the severity of ARDS. The levels of serum CC16, sRAGE, oxygenation index（PaO2/FiO2), acute physiology and chronic health status Ⅱ（APACHEⅡ) scores and sequential organ failure assessment（SOFA) scores were compared between patients with different severity and patients with different disease outcomes, and the correlation between serum CC16, sRAGE levels and PaO2/FiO2, APACHEⅡ scores, SOFA scores and disease outcomes was analyzed. Logistic regression was used to analyze the risk factors of ARDS patients′ death, and ROC curve was used to analyze the predictive value of combined detection and each individual of serum CC16 and sRAGE levels for ARDS patients′ death. Results Comparison of serum CC16, sRAGE levels, and APACHEⅡ, SOFA scores of patients with different degrees of ARDS at admission: the mild group ＜ the moderate group ＜ the severe group, PaO2/FiO2 comparison: the mild group ＞ the moderate group＞ the severe group, the differences were all statistically significant（P＜0. 05); Serum CC16, sRAGE level, and APACHEⅡ, SOFA scores of the dead patients were higher than those of the surviving patients, and PaO2/FiO2 was lower than that of the surviving patients, and the differences were all statistically significant（P＜0. 05); Serum levels of CC16 and sRAGE were negatively correlated with PaO2/FiO2 on admission, and were positively correlatied with APACHEⅡ, SOFA scores, and disease outcome（P＜0. 05). Serum CC16 and sRAGE levels at admission were risk factors for mortality in ARDS patients. Moreover, the ROC area under the curve of combined detection of two index of the ARDS patients was greater than that of each individual index（P＜0. 05). Conclusion The expression of serum CC16 and sRAGE in ARDS patients is up-regulated, which is closely related to disease outcome, and can be used as an effective indicator for early clinical predictive to outcome. [ABSTRACT FROM AUTHOR]

Objective: To analyze the significance of low expression of serum prostate-specific antigen(PSA） and epidermal growth factor(EGF） in patients with different types of benign prostatic hyperplasia(BPH） and their correlation with postoperative disease outcomes. Methods: 128 patients with benign prostatic hyperplasia who received surgical treatment in our hospital from January 2020 to December 2022 were selected as the study objects and grouped according to postoperative pathological biopsy results. Interstitial nodule group(16 cases）, adenomuscular nodule group(32 cases）, fibladenomatous nodule group(12 cases）, glandular nodule group(30 cases）and mixed nodule group(38 cases）, of which 60 cases had interstitial hyperplasia and 68 cases had glandular hyperplasia. The expression levels of serum PSA and EGF in all patients were detected,and the International Prostate Symptom score(IPSS）＜8 six months after surgery was used to determine the prognosis. The difference between serum PSA and EGF in the good prognosis group and the poor prognosis group and the relationship with IPSS score were analyzed. Results: There were differences in serum PSA and EGF expression levels among interstitial nodule group, adenomuscular nodule group, fibladenoma nodule group, glandular nodule group and mixed nodule group(P＜0.05）. The serum levels of PSA and EGF in BPH patients with glandular hyperplasia were significantly higher than those in BPH patients with interstitial hyperplasia(P＜0.05）. ROC curve analysis showed that serum PSA combined with EGF had a sensitivity of 86.42%, specificity of 65.34% and AUC of 0.930 in predicting benign prostatic hyperplasia(BPH）. All patients were followed up for 6 months, with good prognosis in 98 cases and bad prognosis in 30 cases.The expression levels of serum PSA and EGF in the poor prognosis group were significantly higher than those in the good prognosis group(P＜0.05）. According to Pearson correlation analysis, serum PSA and EGF expression levels in BPH patients were negatively correlated with IPSS score(r value was-0.348,-0.417, P value was 0.000）. Conclusion: Serum PSA and EGF are significantly different in patients with different pathologic types of BPH, and the serum PSA and EGF are higher in patients with mainly interstitial hyperplasia and mainly glandular hyperplasia, both of which are closely related to postoperative disease outcomes and deserve clinical attention. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is still a burden to the global health care system, affecting its capacity to maintain essential health services. Even though specific treatment and prevention options are available, the SARS-CoV-2 virus keeps accumulating mutations over time and challenging the efficiency of vaccines, causing new outbreaks and increasing hospitalisation. Early studies suggest that mortality from COVID-19 is increased by age and certain comorbidities. Thus, the goal of this study was to analyse patients hospitalised with COVID-19 pneumonia in terms of age, sex, and comorbidities. Additionally, the influence of treatment with Remdesivir and vaccination on hospitalisation duration and disease outcome was also analysed. The results showed that lethal disease outcome is mainly increased by age and gender, where older and male patients are at a higher risk. There were less deaths in patients with primary arterial hypertension. Other comorbidities did not have a statistically significant influence on disease outcome. Among those who survived, a higher number of patients had been treated with Remdesivir. Vaccination did not have an impact on disease outcome. It could be concluded that older and male patients are the risk group with a worse disease outcome. Treatment with Remdesivir shows a positive effect on disease outcome, although further detailed analysis is necessary. [ABSTRACT FROM AUTHOR]

Glioblastoma, isocitrate dehydrogenase‐wildtype (GB), is the most common and aggressive primary brain malignancy with poor outcome. Immune checkpoint inhibitors (ICIs) have been tested in GB and, despite disappointing results, the identification of a small subgroup of responders underlies the need to improve our understanding of the tumour microenvironment (TME) immunity. This study aimed to determine whether the expression of selected immune checkpoints on tissue‐resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumour samples were collected from 45 patients with histologically confirmed GB (WHO grade 4) and processed to obtain single‐cell suspensions. Patients were assessed for the correlation of Trm phenotype with overall survival (OS) or progression‐free survival (PFS) using multiparametric flow cytometry and uni/multivariate analyses. Levels of Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain‐containing protein 3 (TIM3) were found to be linked to clinical outcome. Low frequency of Trm expressing PD1 or TIM3 or both markers defined subgroups as independent positive prognostic factors for patient survival. On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 were confirmed to be the most predictive independent factors associated with longer OS (hazard ratios—HR [95%CI]: 0.14 [0.04–0.52] p < 0.001, 0.39 [0.16–0.96] p = 0.04, respectively). The CD8+CD103+ Trm subgroups were also age‐related predictors for survival in GB. [ABSTRACT FROM AUTHOR]

Background: The complete blood count (CBC) profile has been found extremely useful in monitoring the growth of SARS-CoV-2 infection; however, predictive CBC parameters that could be used in the management of the disease may vary in different populations. Methods: This study comparatively analyzed the CBC profile of SARS-CoV-2 patients (N=75; confirmed positive by real-time polymerase chain reaction [PCR]) and healthy individuals (confirmed negative by real-time PCR) from Kashmir (North India). Results: Compared with healthy individuals, most of the CBC parameters (hemoglobin levels [13.43 vs 10.9 g/dL; P = 0.0001], lymphocytes [16.04% vs 30.8%; P = 0.00001], monocytes [5.53% vs 7.53%; P = 0.009], and platelet count [150 vs 186 ×103 µL; P = 0.037]) were significantly low in SARS-CoV-2 infected patients, while neutrophilia was more common in infected patients (76.77% vs 59.26%). Among derived parameters, the neutrophil-to-lymphocyte ratio (NLR; 7.31 vs 2.04; P = 0.001) and derived NLR (d-NLR; 4.43 vs 1.5; P = 0.0002) were significantly high in SARS-CoV-2 patients. Further correlation analysis revealed a significant association of neutrophilia with the severity of the disease in SARS-CoV-2 infected patients. Moreover, receiver operating characteristic (ROC) analysis of derived CBC parameters (NLR, d-NLR, and platelet‐to-lymphocyte ratio [PLR] with disease severity and disease outcome) revealed d-NLR as better predictive marker of disease severity (area under the curve [AUC] = 0.658) and disease outcome (AUC = 0.766) compared to PLR with disease severity (AUC = 0.645) and disease outcome (AUC = 0.693). Conclusion: We therefore conclude, of the CBC parameters neutrophilia as the marker of disease severity and among derived parameters, d-NLR as an early predictive biomarker of both disease severity and poor disease outcome in SARS-CoV-2 patients. [ABSTRACT FROM AUTHOR]

Introduction: It is still unknown whether eosinophilic esophagitis (EoE) patients with localized disease are different from those with extended disease. Methods: We evaluated prospectively included patients in the Swiss EoE cohort. Data on all patients with active disease at baseline, no concomitant gastroesophageal reflux disease, no strictures at baseline, and at least one follow-up visit were analyzed. We compared patients with histologically localized proximal versus distal versus extended (=proximal and distal) disease with regard to patient, disease characteristics, disease presentation, and development of complications. Results: We included 124 patients with a median of 2.5 years of follow-up (73.4% males, median age 35.0 years). Ten patients had proximal (8.1%), 46 patients had distal (37.1%), and 68 patients had extended disease (54.8%). Patients with proximal disease were significantly more often females (80%) compared with patients with distal (26.1%, p = 0.002) or extended disease (19.1%, p < 0.001) and reported less severe symptoms (VAS 0 vs. VAS 1, p = 0.001). Endoscopic and histological disease was less pronounced in the proximal esophagus of proximal EoE compared to extended disease (EREFS 1.0 vs. 3.0, p = 0.001; 27.0 eos/hpf vs. 52.5 eos/hpf, p = 0.008). Patients with proximal disease were less likely to undergo dilation compared to patients with distal disease in the follow-up (3.3% vs. 23.3%, p = 0.010). In a multivariate Cox regression model, proximal eosinophilia was less likely to be associated with treatment failure compared to distal eosinophilia. Conclusion: Although isolated proximal EoE is infrequent, it is associated with less severe disease and better disease outcome. Proximal disease appears to present a unique EoE phenotype. [ABSTRACT FROM AUTHOR]

Zupeng Xiao, Hanyi Wu, Xin Chen, Xiaoli Chen, Rentao Yu, Aijun Chen Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Aijun Chen; Rentao Yu, Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 13062377863; +86-18123303562, Email chenaijun@hospital.cqmu.edu.cn; rentaoyu@hotmail.comPurpose: Herpes zoster ophthalmicus (HZO) causes trouble in patients’ daily life and work. In severe cases, it may even lead to a decrease or loss of vision. To understand the demographic information and ocular symptoms of hospitalized patients with HZO, and to find potential factors related to improvement time of skin rash and duration of ocular symptoms at discharge, we design this study.Patients and Methods: This is a retrospective study. All patients diagnosed with HZO who were hospitalized in the Department of Dermatology of a hospital in Chongqing, China from January 1, 2015 to December 30, 2021 were included in this study. A total of 189 patients were included in this study. Clinical manifestations of the disease during hospitalization, improvement time of ocular skin lesions, and whether ocular skin lesions disappeared completely at discharge were recorded.Results: The most common ocular symptom was eyelid swelling (92.6%), followed by eye pain (48.7%). The most common ocular sign was conjunctivitis (78.3%), followed by keratitis (15.9%). There were 149 cases without residual ocular symptoms and 40 cases with residual ocular symptoms. There was no statistically significant difference in demographic characteristics between the two groups (P> 0.05). Age ≥ 70 years (B=0.381, − 0.061~0.022, P=0.005), use of glucocorticoids (B=0.260, 0.024~0.496, P=0.031), and use of topical antiviral drugs (B=0.380, 0.054~0.705, P=0.023) were factors affecting the time interval from admission to improvement of skin rash. Tearing (HR, OR=4.827, 1.956~11.909, P< 0.001) and blood urea nitrogen (OR=0.787, 0.620– 1.000, P=0.050) were factors influencing residual ocular symptoms.Conclusion: This study could help clinicians gain a deeper understanding of the clinical manifestations and partial influencing factors of HZO patients, which may contribute to future clinical work.Keywords: herpes zoster ophthalmicus, clinical manifestations, disease outcome, risk factors

Cardiovascular pathology can complicate the course of COVID-19. The study aimed to identify echocardiographic abnormalities and key prognostic factors influencing severe and fatal COVID-19 outcomes. This retrospective cohort study included clinical and echocardiogram data from 194 medical records of hospitalized patients with COVID-19: 100 moderate cases, 34 severe cases with favorable outcomes, and 60 severe cases with fatal outcomes. Severe patients with favorable outcomes had greater reductions in left ventricular systolic fraction of left ventricle compared to moderate cases (23.5% vs. 7.0%, respectively, p=0.008) and ejection fraction of left ventricle (14.7% vs. 3.0%, respectively, p=0.013), grade I diastolic dysfunction of the left ventricle (20.6% vs. 8.0%, respectively, p=0.044), and pulmonary hypertension (29.41% vs. 10.0%, respectively, p=0.006). Patients with fatal outcomes had a mean age of 67.1±1.51 years, chronic heart failure functional class II (58.3%), hypertension (50.0%), type 2 diabetes (43.3%), and obesity (33.3%). Compared to severe cases but with favorable outcomes, fatal cases had a greater decrease in left ventricular ejection fraction (36.7% vs. 14.7%, respectively, p=0.024), various types of myocardial dysfunction (51.7% vs. 29.4%, respectively, p=0.037) and a trend towards increased pulmonary hypertension (48.3% vs. 29.4%, respectively, p=0.074). Consequently, chronic heart failure class II, reduced left ventricular ejection fraction, various myocardial dysfunctions, and pulmonary hypertension emerged as key cardiac risk factors for severe disease progression and mortality in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-infection is associated with an extremely variable disease course. When interstitial pneumonia (IP) occurs, it can lead to acute respiratory distress syndrome and death. Serum Krebs von den Lungen-6 (KL-6) is an established marker of IP, but its role as a marker of SARS-CoV-2 pneumonia is debated. This bicentric study included 157 patients with SARS-CoV-2 pneumonia. The WHO Ordinal Scale for Clinical Improvement (0–10 points) was used to classify the clinical course. Serum samples were collected at admission, and on days 3 and 7 of hospitalization. KL-6 was measured by using automated chemiluminescence immunoassay. A total of 68 patients developed a severe SARS-CoV-2 pneumonia, 135 of them required oxygen, and 15 died during hospitalization. The patients requiring non-invasive ventilation, invasive ventilation, or extracorporeal membrane oxygenation had significantly higher serum KL-6 levels at admission. The serum KL-6 levels were tendentially higher in patients who died than in those who survived. Logistic regression identified serum KL-6 at a cut-off of 335 U/mL at admission as a significant predictor of severe SARS-CoV-2 pneumonia outcome. Serum KL-6 seems to be a candidate biomarker for the clinical routine to stratify patients with SARS-CoV-2 pneumonia for the risk of a severe disease outcome or death. [ABSTRACT FROM AUTHOR]

Transforming growth factor beta (TGF-β) is a ubiquitously distributed cytokine known to contribute to the pathogenesis of numerous pathological processes. The aim of this study was to measure serum concentrations of TGF-β1 in severely ill COVID-19 patients and to analyze its relationship with selected hematological and biochemical parameters and with the disease outcome. The study population included 53 COVID-19 patients with severe clinical expression of the disease and 15 control subjects. TGF-β1 was determined in serum samples and supernatants from PHA-stimulated whole blood cultures using ELISA assay. Biochemical and hematological parameters were analyzed using standard accepted methods. Our results showed that serum levels of TGF-β1 in COVID-19 patients and controls correlate with the platelet counts. Also, positive correlations of TGF-β1 with white blood cell and lymphocyte counts, platelet-to-lymphocyte (PLR) ratio, and fibrinogen level were shown, while negative correlations of this cytokine with platelet distribution width (PDW), D-dimer and activated partial thromboplastin time (a-PTT) values in COVID-19 patients were observed. The lower serum values of TGF-β1 were associated with the unfavorable outcome of COVID-19. In conclusion, TGF-β1 levels were strongly associated with platelet counts and unfavorable disease outcome of severely ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

Abstract Background Idiopathic non-clonal cytopenia (ICUS) and clonal cytopenia (CCUS) are common in the elderly population. While these entities have similar clinical presentations with peripheral blood cytopenia and less than 10% bone marrow dysplasia, their malignant potential is different and the biological relationship between these disorders and myeloid neoplasms such as myelodysplastic syndrome (MDS) is not fully understood. Aberrant DNA methylation has previously been described to play a vital role in MDS and acute myeloid leukemia (AML) pathogenesis. In addition, obesity confers a poorer prognosis in MDS with inferior overall survival and a higher rate of AML transformation. In this study, we measured DNA methylation of the promoter for the obesity-regulated gene LEP, encoding leptin, in hematopoietic cells from ICUS, CCUS and MDS patients and healthy controls. We investigated whether LEP promoter methylation is an early event in the development of myeloid neoplasms and whether it is associated with clinical outcome. Results We found that blood cells of patients with ICUS, CCUS and MDS all have a significantly hypermethylated LEP promoter compared to healthy controls and that LEP hypermethylation is associated with anemia, increased bone marrow blast percentage, and lower plasma leptin levels. MDS patients with a high LEP promoter methylation have a higher risk of progression, shorter progression-free survival, and inferior overall survival. Furthermore, LEP promoter methylation was an independent risk factor for the progression of MDS in a multivariate Cox regression analysis. Conclusion In conclusion, hypermethylation of the LEP promoter is an early and frequent event in myeloid neoplasms and is associated with a worse prognosis.

Objective: This study aimed to evaluate the clinical characteristics of children diagnosed with juvenile dermatomyositis (JDM) in a tertiary medical centre in Taiwan and to identify important biomarkers for predicting the disease course and outcomes of JDM. Methods: We retrospectively reviewed patients with JDM diagnosed at the National Taiwan University Hospital between 1 January 2001 and 31 December 2021. The endpoints for disease assessment included complete clinical response or remission. The JDM courses were divided into monocyclic, polycyclic, and chronic continuous statuses. The significant relationship between the predictors and outcomes was further analysed. Results: A total of 47 patients were included in this study. The mean age at disease onset was 7.5 years. The female-to-male ratio was 1.35. The most common initial presentations were Gottron's sign (74%), followed by muscle weakness (66%) and facial rash (66%). Among all included patients, 35 (74.5%) patients achieved complete clinical remission, 15 (31.9%) had a monocyclic course, six (12.7%) had a polycyclic course, and 24 (51.1%) had a chronic continuous course. Negative facial rash and arthralgia were favourable factors for achieving complete clinical remission. Muscle weakness, higher lactate dehydrogenase (LDH), and higher erythrocyte sedimentation rate (ESR) at disease onset were related to the chronic continuous course. The most common long-term complication was calcinosis (29.8%). Conclusion: Juvenile dermatomyositis is a rare disease, and only a few studies have been conducted in Asia. Our results identified the important predictors of the disease course and outcomes. The chronic continuous course requires more attention and aggressive treatment.

Background During the American epidemic, Zika virus (ZIKV) expanded rapidly through dengue virus (DENV)-endemic regions. We analyzed the presentation of ZIKV infection in patients from the City of Orán, Argentina, and compared some of its features with dengue presentation in the same region. Methods A retrospective study was conducted at San Vicente de Paul Hospital during 2016–2018. Clinical and demographic characteristics, pre-existing immunity to DENV, viral load and type I interferon (IFN) responses were studied in 63 patients with ZIKV infection. Results Clinical manifestations of ZIKV infection were generally mild compared with dengue, although rash (p<0.001) and itching (p<0.001) were significantly more prevalent in ZIKV patients. ZIKV patients aged <15 y manifested relatively mild disease compared with older ZIKV patients, showing a decreased prevalence of headache (p=0.008), retro-orbital pain (p=0.001) and arthralgia (p=0.001). Increased Zika incidence was observed in female patients (60.3%). Serum viral load was low to undetectable in ZIKV patients and was not associated with serum anti-DENV IgG titers. Interferon-α and IFN-β serum levels did not correlate with serum viral load in ZIKV patients. Conclusions Clinical presentation of ZIKV and DENV infections is largely overlapping, presenting a challenge for diagnosis and risk assessment for uniquely at-risk populations. [ABSTRACT FROM AUTHOR]

Background and Objectives: Early reports on COVID-19 infection suggested that the SARS-CoV-2 virus solely attacks respiratory tract cells. As the pandemic spread, it became clear that the infection is multiorganic. Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease strongly associated with insulin resistance and diabetes. The aim of this study was to assess a possible interplay between MAFLD and COVID-19 infection and its implication in COVID-19 outcome. Materials and Methods: A retrospective observational study, including 130 COVID-19 positive patients was conducted. MAFLD diagnosis was made based on the International Consensus criteria. Patients were divided into two groups, group A (MAFLD) and group B (nonMAFLD). Anthropometric and laboratory analysis were obtained. COVID-19 severity was assessed using the NEWS2 score. Disease outcome was threefold and regarded as discharged, patients who required mechanical ventilation (MV), and deceased patients. Results: MAFLD prevalence was 42%, 67% of patients were discharged, and 19% needed MV. Mortality rate was 14%. MAFLD patients were significantly younger (p < 0.001), and had higher body mass index (p < 0.05), respiratory rate (p < 0.05) and systolic blood pressure (p < 0.05) than nonMAFLD patients. Regarding metabolic syndrome and inflammatory markers: group A had significantly higher glycemia at admission (p = 0.008), lower HDL-c (p < 0.01), higher triglycerides (p < 0.01), CRP (p < 0.001), IL-6 (p < 0.05) and ferritin (p < 0.05) than group B. MAFLD was associated with more prevalent type 2 diabetes (p = 0.035) and hypertension (p < 0.05). MAFLD patients had a more severe disease course (NEWS2 score, 6.5 ± 0.5 vs. 3 ± 1.0, p < 0.05). MAFLD presence was associated with lower patient discharge (p < 0.01) and increased need for MV (p = 0.024). Multiple regression analysis showed that BMI (p = 0.045), IL-6 (p = 0.03), and MAFLD (p < 0.05) are significant independent risk factors for a poor COVID-19 outcome. Conclusions: The prevalence of MAFLD is relatively high. MAFLD patients had a more severe COVID-19 clinical course and worse disease outcome. Our results imply that early patient stratification and risk assessment are mandatory in order to avoid poor outcomes. [ABSTRACT FROM AUTHOR]

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p

The severity of the 2019 coronavirus disease (COVID-19) and its effects remain unpredictable. Certain factors, such as obesity, hypertension, and type 2 diabetes mellitus, may increase the severity of the disease. Rheumatology experts suggest that patients with active autoimmune conditions and controlled autoimmune diseases on immunosuppressive therapy may be at higher risk of developing severe COVID-19. In this retrospective observational study, we aimed to examine the patterns of COVID-19 in patients with underlying rheumatological diseases and their association with disease severity and hospital outcomes. A total of 34 patients with underlying rheumatological diseases who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR) were included between March 2020 and April 2021 at King Fahd Hospital of the University. The study population consisted of 76.47% female and 23.53% male patients, with a mean age ranging from 20 to 40 years. Female gender (p=0.0001) and younger age (p=0.004) were associated with milder disease. The most frequent rheumatological disease was systemic lupus erythematosus (SLE) (38.24%), which was associated with a milder infection (p=0.045). Patients treated with mycophenolate mofetil (MMF) had a milder disease course (p=0.0037). Hypertension was significantly associated with severe COVID-19 disease (p=0.037). There was no significant relationship between SLE and the need for ICU admission. Patients on hydroxychloroquine and MMF tended to develop milder disease, and there was no association between the severity of the infection and the treatment with steroids. [ABSTRACT FROM AUTHOR]

• Heart failure is one of the most common cardiovascular disorders. • Heart failure affects physical, physiological, and social activities. • Insufficient knowledge can lead to inadequate self-care and disease progression • The Haddon matrix identifies and analyzes risk factors to reduce disease consequences. Heart failure affects the physical, physiological, social, and activities of individuals. The study aimed to teach preventive behavior with Haddon strategy on self-care behavior and the consequences of heart failure. In this clinical trial, 96 patients with heart failure were randomly assigned to two groups. The Haddon group was educated with Haddon prevention strategies three times a week, for 60 minutes. A demographic questionnaire, self-care index, and consequences checklist were filled in both groups at the start of the study, discharge time, and one month after the last training session. Statistical analysis was done using independent t-test, paired t-test, chi-square, Fisher and analysis of covariance, Friedman, and Cochran Q in SPSS with version 23. Self-care behavior in the Haddon group after training significantly increased (p < 0.001). Disease consequences were significantly reduced in the Haddon group after training (p < 0.05). The consequences of the disease in Haddon group decreased during 4 weeks of monitoring and the changes were significant (p < 0.001). It is suggested that this educational method could be used to increase self-care behavior, prevent hospitalizations, decrease symptoms, and improve quality of life for patients with heart failure. Nurses can identify and manage risk factors for heart disease using the Haddon strategy. [ABSTRACT FROM AUTHOR]

Background: Idiopathic non-clonal cytopenia (ICUS) and clonal cytopenia (CCUS) are common in the elderly population. While these entities have similar clinical presentations with peripheral blood cytopenia and less than 10% bone marrow dysplasia, their malignant potential is different and the biological relationship between these disorders and myeloid neoplasms such as myelodysplastic syndrome (MDS) is not fully understood. Aberrant DNA methylation has previously been described to play a vital role in MDS and acute myeloid leukemia (AML) pathogenesis. In addition, obesity confers a poorer prognosis in MDS with inferior overall survival and a higher rate of AML transformation. In this study, we measured DNA methylation of the promoter for the obesity-regulated gene LEP, encoding leptin, in hematopoietic cells from ICUS, CCUS and MDS patients and healthy controls. We investigated whether LEP promoter methylation is an early event in the development of myeloid neoplasms and whether it is associated with clinical outcome. Results: We found that blood cells of patients with ICUS, CCUS and MDS all have a significantly hypermethylated LEP promoter compared to healthy controls and that LEP hypermethylation is associated with anemia, increased bone marrow blast percentage, and lower plasma leptin levels. MDS patients with a high LEP promoter methylation have a higher risk of progression, shorter progression-free survival, and inferior overall survival. Furthermore, LEP promoter methylation was an independent risk factor for the progression of MDS in a multivariate Cox regression analysis. Conclusion: In conclusion, hypermethylation of the LEP promoter is an early and frequent event in myeloid neoplasms and is associated with a worse prognosis. [ABSTRACT FROM AUTHOR]

Changes in the immune system participate in the pathogenesis and development of infectious diseases. Previous studies have indicated immune dysregulation in patients suffering from COVID-19 and mucormycosis. Therefore, this study investigated whether interleukin-27 (IL-27) and interleukin-32 (IL-32) levels may participate in the development and outcome of COVID-19 associated mucormycosis (CAM). The blood samples were obtained from 79 patients suffering from COVID-19 and mucormycosis and 25 healthy subjects. The serum samples were isolated from the whole blood and frequencies of some immune cells were measured by a cell counter. The levels of IL-27 and IL-32 were assessed by enzyme-linked immunosorbent assay. IL-27 and IL-32 levels were significantly lower in patients with COVID-19 and mucormycosis than healthy subjects (P <.05), although there was no significant difference in IL-27 between patients with COVID-19 and CAM. IL-27 level was significantly higher in severe COVID-19 survivors than dead cases (P <.01). Patients with CAM had significant increases in NLR compared to COVID-19 patients and healthy individuals (P <.0001–0.01). NLR was significantly associated with COVID-19 outcome (P <.05). Severe COVID-19 survivors had a significant reduction in NLR compared to non-survivors (P <.05). Changes in IL-27 and IL-32 levels may contribute to the pathogenesis of CAM. IL-27 may relate to the pathogenesis and outcomes of mucormycosis in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background and aim: Having weakness and lethargy and feeling the need for hospital emergency services is one of the most important reasons for patients to go to hospital emergency rooms. The aim of the present study was to investigate the relationship between morbidity and mortality of patients with weakness and lethargy. Method: The present study was conducted in an observational and prospective manner in the emergency department of Rasool Akram and Firouzgar hospitals. The patients were divided into 5 groups by the evaluation team in the emergency triage unit using the international valid triage tool "Emergency Severity Index (ESI)". The patients were followed up for 2 months after the time of discharge and the patient's condition was examined in terms of illness, health or death. Result: Between levels 1 and 2 (patients with high severity conditions) and 3 (patient needs two or more emergency facilities in case of no disturbance in vital signs), level 3 had the highest frequency of referrals (61.9%). 90.7% had an underlying disease and 66.1% of the patients were taking medication at the time of visit. 11% of patients died in the first visit. In the initial follow-up, 23.7% of people were still sick, 40.7% had recovered and 17.8% had died. Conclusion: According to results in the final follow-up, 3.9% of people were still sick; the rate of recovered patients in the final follow-up was 44.1% and the percentage of deaths in the final follow-up was 24.6%. The high mortality rate indicates that the patients' concern was not due to weakness and lethargy, but due to a dangerous underlying disease that forced them to go to the hospital.

The aim of our study was to investigate the main characteristics of peripheral blood NKT cell phenotype in patients with disseminated purulent peritonitis (DPP) in dynamics of postoperative period, depending on the disease outcome. Fifty-two patients with acute surgical diseases and injuries of the abdominal organs complicated by DPP, and 68 healthy individuals in control group, were examined. Blood sampling was performed before surgery (preoperative period), as well as on the day 7, 14 and 21 of postoperative period. All patients with DPP were divided into two groups depending on disease outcome in postoperative period: patients with favorable disease outcome (n = 34); and patients with unfavorable outcome (n = 18). Study of the phenotype of blood NKT lymphocytes was performed by flow cytometry using direct immunofluorescence of whole peripheral blood samples with monoclonal antibodies. The low relative and absolute level of NKT cells was observed in DPP patients regardless of outcome disease in preoperative period. At the same time, the absolute level of NKT cells returned to normal only in patients with favorable DPP outcome and only by day 21 after surgery. Patients with favorable DPP outcome by the end of examination period had normalized quantity of mature NKT-lymphocytes and significantly decreased level of cytotoxic cells which was apparently associated with migration of such cell subsets to site of inflammation. A reduced level of non-classical (expressing CD8 marker) mature and cytokine-producing NKT cells was detected only in patients with favorable DPP outcome in preoperative period which returned to normal by the end of postoperative period. At the same time, patients with unfavorable disease outcome had reduced quantity of NKT cells of these subsets by day 21 of postoperative treatment. Patients with favorable outcome had high level of mature and cytotoxic CD11b+ NKT cells already in the preoperative period, while patients with unfavorable DPP outcome had increased level of cytotoxic CD11b+ NKT cells only by day 21 after surgery. The proportion of NKT cells expressing activation markers (CD28 and CD57) was reduced in patients in preoperative period that returned to normal immediately after surgery with favorable outcome, while it recovered with unfavorable outcome closer to the end of postoperative examination. The defined features of NKT cell phenotype in patients with unfavorable DPP outcome characterize disturbances in subset ratio and mechanisms of functioning of this cell fraction. This determines a need to develop immunotherapeutic methods aimed at stimulating immunoregulatory activity of NKT cells.

Objective: To study the influencing factors of high nutritional risk in children with sepsis and their effects on immune function, trace elements and disease outcome. Methods: 168 children with sepsis who were admitted to our hospital from January 2019 to December 2021 were selected, the nutritional status and growth risk screening tool (STRONGkids) was used to screen their nutritional risk, according to the scoring results, the children with nutritional risk were divided into medium-low nutritional risk group and high nutritional risk group. The clinical data of the two groups were compared, and the influencing factors of high nutritional risk were analyzed by Logistic regression model. The indexes of immune function (CD4+, CD8+, CD4+/CD8+), the contents of trace elements [copper (Cu), iron (Fe), zinc (Zn)] and the disease outcome situation were compared between the low and middle nutrition risk group and the high nutrition risk group. Results: The results of STRONGkids nutritional risk screening showed that 151 children with sepsis had nutritional risk, and the incidence of nutritional risk was 89.88%, including 110 cases of medium-low nutritional risk (medium-low nutritional risk group) and 41 cases of high nutritional risk (high nutritional risk group). The acute physiology and chronic health score system II (APACHE II) score, lactic acid, procalcitonin levels and the proportion of severe sepsis in the high nutritional risk group were higher than those in the medium-low nutritional risk group, and the albumin level was lower than that in the medium-low nutritional risk group (P<0.05). Multivariate Logistic regression analysis showed that increased APACHE II score and severe sepsis were risk factors for high nutritional risk in children with sepsis (P<0.05), and increased albumin was a protective factor for high nutritional risk in children with sepsis (P<0.05). CD4+ and CD4+/CD8+ in the high nutritional risk group were lower than those in the medium-low nutritional risk group, and CD8+ was higher than that in the medium-low nutritional risk group (P＜0.05). There was no significant difference in Cu content between the two groups (P>0.05). The Fe and Zn contents in the high nutritional risk group were lower than those in the medium-low nutritional risk group (P＜0.05). There were 74 cases of improvement, 32 cases of unrecovery, and 4 cases of death in the medium-low nutritional risk group, while 19 cases of improvement, 15 cases of unrecovery and 7 cases of death in the high nutritional risk group, the good disease outcome rate in the high nutritional risk group was lower than that in the medium-low nutritional risk group (P＜0.05). Conclusion: The incidence of high nutritional risk is high in children with sepsis. Severe sepsis, APACHE Ⅱ score and albumin level are the influencing factors of high nutritional risk, and high nutritional risk leads to the decline of immune function, the reduction of Fe and Zn content in the body, and poor disease outcome. Early nutritional intervention is recommended to improve the prognosis of children. [ABSTRACT FROM AUTHOR]

Objective To assess variability in care quality and treatment outcomes across ethnicities in early inflammatory arthritis (EIA). Methods We conducted an observational cohort study in England and Wales from May 2018 to March 2020, including patients with a suspected/confirmed EIA diagnosis. Care quality was assessed against six metrics defined by national guidelines. Clinical outcomes were measured using DAS28. Outcomes between ethnic groups ('White', 'Black', 'Asian', 'Mixed', 'Other') were compared, and adjusted for confounders. Results A total of 35 807 eligible patients were analysed. Of those, 30 643 (85.6%) were White and 5164 (14.6%) were from ethnic minorities: 1035 (2.8%) Black; 2617 (7.3%) Asian; 238 (0.6%) Mixed; 1274 (3.5%) Other. In total, 12 955 patients had confirmed EIA, of whom 11 315 were White and 1640 were from ethnic minorities: 314 (2.4%) Black; 927 (7.1%) Asian; 70 (0.5%) Mixed; 329 (2.5%) Other. A total of 14 803 patients were assessed by rheumatology within three weeks, and 5642 started treatment within six weeks of referral. There were no significant differences by ethnicity. Ethnic minority patients had lower odds of disease remission at three months [adjusted odds ratio 0.79 (95% CI: 0.65, 0.96)] relative to White patients. Ethnic minorities were significantly less likely to receive initial treatment withMTX[0.68 (0.52, 0.90)] or with glucocorticoids [0.63 (0.49, 0.80)]. Conclusion We demonstrate that some ethnic minorities are less likely to achieve disease remission in three months following EIA diagnosis. This is not explained by delays in referral or time to treatment. Our data highlight the need for investigation into the possible drivers of these inequitable outcomes and reappraisal of EIA management pathways. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-infection is associated with an extremely variable disease course. When interstitial pneumonia (IP) occurs, it can lead to acute respiratory distress syndrome and death. Serum Krebs von den Lungen-6 (KL-6) is an established marker of IP, but its role as a marker of SARS-CoV-2 pneumonia is debated. This bicentric study included 157 patients with SARS-CoV-2 pneumonia. The WHO Ordinal Scale for Clinical Improvement (0–10 points) was used to classify the clinical course. Serum samples were collected at admission, and on days 3 and 7 of hospitalization. KL-6 was measured by using automated chemiluminescence immunoassay. A total of 68 patients developed a severe SARS-CoV-2 pneumonia, 135 of them required oxygen, and 15 died during hospitalization. The patients requiring non-invasive ventilation, invasive ventilation, or extracorporeal membrane oxygenation had significantly higher serum KL-6 levels at admission. The serum KL-6 levels were tendentially higher in patients who died than in those who survived. Logistic regression identified serum KL-6 at a cut-off of 335 U/mL at admission as a significant predictor of severe SARS-CoV-2 pneumonia outcome. Serum KL-6 seems to be a candidate biomarker for the clinical routine to stratify patients with SARS-CoV-2 pneumonia for the risk of a severe disease outcome or death.

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed. [ABSTRACT FROM AUTHOR]

• Adjuvant ICI increased symptomatic pulmonary adverse events. • Adjuvant ICI improved survival and disease control. • Pulmonary adverse events were the major cause of ICI discontinuation. • Discontinuation of ICI led to poorer survival and distant disease control. We compared treatment-related pulmonary adverse events (TRPAE), progression-free survival (PFS), and overall survival (OS) among locally advanced non-small cell lung cancer (NSCLC) patients who received concurrent chemoradiotherapy (CRT) versus CRT followed by immune check point inhibitor (ICI) immunotherapy (CRTI). TRPAE was defined as any pulmonary events as defined in CTCAE v.5 occurring within 12 months after completion of radiotherapy. Outcomes were compared between CRT and CTRI by Cox proportional hazard regression and Kaplan-Meier analyses. We also assessed if TRPAE-induced discontinuation of ICI affected survival. We analyzed 326 patients treated between July 2010 and November 2019; 195 patients received CRT and 131 received CRTI. The incidences of severe grade ≥ 3 TRPAE were similar between the two groups, however, symptomatic TRPAE was almost doubled in CRTI group (65.7 % CTRI vs 35.9 % CRT, P < 0.0001). The rates of 4-year OS and PFS were 54.5 % vs 36.7 % (P = 0.0003) and 43.8 % vs 35.8 % (P = 0.038) in CRT + Durvalumab and CRT group, respectively. Receipt of ICI Durvalumab was associated with better 4-year OS (HR 0.53, 95 % CI 0.36–0.78, P = 0.001) and PFS (HR 0.55, 95 % CI 0.38–0.80, P = 0.002). Patients who discontinued ICI because of TRPAE had worse 4-year OS (P = 0.001) and higher rates of distant metastasis (P = 0.003) than those who completed planned ICI after developing TRPAE. CRT followed by adjuvant ICI led to improved 4-year OS and PFS consistent with published data. CRTI was associated with higher incidence of grade ≥ 2 TRPAE in both high and low mean lung dose groups without significant difference in grade ≥ 3 TRPAE. Discontinuation of ICI due to TRPAE was associated with poorer OS and distant disease control than completing ICI as planned after developing TRPAE. [ABSTRACT FROM AUTHOR]

Objectives The clinical progression of JIA is unpredictable. Knowing who will develop severe disease could facilitate rapid intensification of therapies. We use genetic variants conferring susceptibility to JIA to predict disease outcome measures. Methods A total of 713 JIA patients with genotype data and core outcome variables (COVs) at diagnosis (baseline) and 1 year follow-up were identified from the Childhood Arthritis Prospective Study (CAPS). A weighted genetic risk score (GRS) was generated, including all single nucleotide polymorphisms (SNPs) previously associated with JIA susceptibility (P -value < 5×10−08). We used multivariable linear regression to test the GRS for association with COVS (limited joint count, active joint count, physician global assessment, parent/patient general evaluation, childhood HAQ and ESR) at baseline and change in COVS from baseline to 1 year, adjusting for baseline COV and International League of Associations of Rheumatology (ILAR) category. The GRS was split into quintiles to identify high (quintile 5) and low (quintile 1) risk groups. Results Patients in the high-risk group for the GRS had a younger age at presentation (median low risk 7.79, median high risk 3.51). No association was observed between the GRS and any outcome measures at 1 year follow-up or baseline. Conclusion For the first time we have used all known JIA genetic susceptibility loci (P =<5×10−08) in a GRS to predict changes in disease outcome measured over time. Genetic susceptibility variants are poor predictors of changes in core outcome measures, it is likely that genetic factors predicting disease outcome are independent to those predicting susceptibility. The next step will be to conduct a genome-wide association analysis of JIA outcome. [ABSTRACT FROM AUTHOR]

Background: Reports describing demographics, clinical characteristics, hospital course, morbidity, and mortality in patients in the Indian setting have been published, but they are based on limited numbers of cases. The present study among the patients with known outcomes enabled us to better understand the disease process and progression of COVID-19 cases and to correlate the factors affecting the outcome. Methods: This was a record-based, retrospective observational study of patients admitted to COVID-19 Hospital. We have retrieved medical records for all the hospitalized patients with a laboratory confirmed COVID-19 diagnosis with a known outcome (discharged or died) between April 1, 2020 and February 28, 2021. The extracted data included basic demographics, signs and symptoms, duration of hospitalization, and laboratory parameters. Categorical variables were analysed using either the chisquare test or Fisher's exact test. The level of significance was set at P < 0.05. Results: The mean age of severe and moderate patients was 38.71 years, compared to 34.95 years for mild patients. No gender difference was observed for the severe/moderate, and mild cases. The mortality rate among severe/moderate cases was 11.6%, whereas it was 3.9% in mild patients. Laboratory parameters which were significantly (p < 0.05) raised among the dead compared to discharged patients included CT score, D-dimer, CRP, ALT, AST, and alkaline phosphatase. Conclusion: Clinical and laboratory characteristics reflect the pathophysiology of disease and thus help clinicians recognise the severity of medical illness. They also facilitate the creation of management protocols for clinical care that results in improvement in patient related outcomes. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a major global health challenge that has affected all age groups and gender, with over 5 million deaths reported worldwide to date. The objective of this study is to assess available information on COVID-19 in children and adolescents with respect to clinical characteristics, co-morbidities, and outcomes, and identify gaps in the literatures for appropriate actions. Methodology: Electronic databases including Web of Science, PubMed, Scopus, and Google Scholar were searched for observational studies such as case series, cross-sectional and cohort studies published from December 2019 to September 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide. Data extracted included (i) patient demography (age and gender), (ii) clinical characteristics including vaccination status and presence of co-morbidities, (iii) clinical management including the use of sequential organ failure assessment (SOFA) scores, oxygen requirement, use of mechanical ventilation, and (iv) disease outcomes including length of hospital and intensive care unit (ICU) admission, recovery, complications with sequelae, or death. Data were analyzed using descriptive statistics. Results: A total of 11 eligible studies were included with a total of 266 children and adolescents; 137 (51.5%) females and 129 (48.5%) males. The mean age of the children was 9.8 years (range of 0 - 19 years), and children = 6 years were more affected (40.7%) than age groups 1 - 5 years (31.9%) and < 1 year (27.4%). The major co-morbidities were respiratory diseases including pre-existing asthma (3.4%), neurologic conditions (3.4%) and cardiac pathology (2.3%). Majority (74.8%, 199/266) of the patients were discharged without sequelae, 0.8% (2/266) were discharged with sequalae from one study, and mortality of 1.9% (5/266) was reported, also from one study. SOFA scores of patients at admission were not stated in any of the study, while only one study reported patient vaccination status. Conclusion: It is recommended that safe vaccines for children < 1 year of age should be developed in addition to other preventive measures currently in place. SOFA scores should be used to assess risk of COVID-19 severity and monitor prognosis of the disease, and vaccination status of children should be documented as this may impact the management and prognosis of the disease. [ABSTRACT FROM AUTHOR]

The role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the pandemic context of coronavirus disease 2019 (COVID-19) continues to be debated. Patients with hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease, or chronic obstructive pulmonary disease (COPD), who often use ACEi/ARB, may be at risk of severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population. This study is an observational study of patients with a positive severe acute respiratory syndrome coronavirus 2 test and inpatient treatment at a healthcare facility, using the registry information of COVIREGI-JP. Our primary outcomes were in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and intensive care unit admission. Out of the 6055 patients, 1921 patients with preexisting hypertension, diabetes mellitus, chronic renal failure, cerebro-cardiovascular disease, or COPD were enrolled. Factors associated with an increased risk of the primary outcomes were aging, male sex, COPD, severe renal impairment, and diabetes mellitus. No correlations were observed with ACEi/ARB, cerebro-cardiovascular diseases, or hypertension. Associated factors in male patients were aging, renal impairment, hypertension, and diabetes. In female patients, factors associated with an increased risk were aging, ACEi/ARB, renal impairment, and diabetes, whereas hypertension was associated with a lower risk of the primary outcomes. Independent factors for the primary outcomes were aging, male sex, COPD, severe renal impairment, and diabetes, but not ACEi/ARB. Based on this registry data analysis, more detailed data collection and analysis is needed with the cooperation of multiple healthcare facilities. [Display omitted] • Coronavirus disease 2019 patients with hypertension (HT), diabetes mellitus (DM), chronic kidney disease (CKD), cardiovascular disease, or chronic obstructive pulmonary disease (COPD) from COVIREGI-JP were evaluated. • Outcomes consisted of in-hospital death, ventilator support, extracorporeal membrane oxygenation, and intensive care unit admission. • Related factors for outcomes were aging, male, COPD, CKD, and DM, but not angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB). • In male patients, related factors for outcomes were aging, CKD, HT, and DM. • In female patients, increased risk factors were aging, ACEi/ARB, CKD, and DM. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objective: This study aims to investigate the association between smoking and the severity of COVID-19 infection during the initial wave of this pandemic in Malaysia. Methods: This is a multi-center observational study using secondary hospital data collected retrospectively from February 1, 2020, until May 30, 2020. Clinical records of all real-time polymerase chain reaction (RT-PCR)-confirmed COVID-19 cases with smoking status, co-morbidities, clinical features, and disease management were retrieved. Severity was assessed by the presence of complications and outcomes of COVID-19 infection. Logistic regression was used to determine the association between COVID-19 disease severity and smoking status. Results: A total of 5,889 COVID-19 cases were included in the analysis. Ever smokers had a higher risk of having COVID-19 complications, such as acute respiratory distress syndrome (odds ratio [OR] 1.69; 95% confidence interval [CI] 1.09-2.55), renal injury (OR 1.55; 95% CI 1.10-2.14), and acute liver injury (OR 1.33; 95% CI 1.01-1.74), compared with never smokers. However, in terms of disease outcomes, there were no differences between the two groups. Conclusion: Although no significant association was found in terms of disease outcomes, smoking is associated with a higher risk of having complications owing to COVID-19 infection.

Background: Reports describing demographics, clinical characteristics, hospital course, morbidity, and mortality in patients in the Indian setting have been published, but they are based on limited numbers of cases. The present study among the patients with known outcomes enabled us to better understand the disease process and progression of COVID-19 cases and to correlate the factors affecting the outcome. Methods: This was a record-based, retrospective observational study of patients admitted to COVID-19 Hospital. We have retrieved medical records for all the hospitalized patients with a laboratory confirmed COVID-19 diagnosis with a known outcome (discharged or died) between April 1, 2020 and February 28, 2021. The extracted data included basic demographics, signs and symptoms, duration of hospitalization, and laboratory parameters. Categorical variables were analysed using either the chisquare test or Fisher's exact test. The level of significance was set at P < 0.05. Results: The mean age of severe and moderate patients was 38.71 years, compared to 34.95 years for mild patients. No gender difference was observed for the severe/moderate, and mild cases. The mortality rate among severe/moderate cases was 11.6%, whereas it was 3.9% in mild patients. Laboratory parameters which were significantly (p < 0.05) raised among the dead compared to discharged patients included CT score, D-dimer, CRP, ALT, AST, and alkaline phosphatase. Conclusion: Clinical and laboratory characteristics reflect the pathophysiology of disease and thus help clinicians recognise the severity of medical illness. They also facilitate the creation of management protocols for clinical care that results in improvement in patient related outcomes.

The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1–4, 5–11, 12–16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities. • This study illustrates the findings from the international HyperPedCovid registry collecting 1009 patients with MIS-C and describing variations in the clinical presentation and management across different ages and geographical regions. • Patients from limited resources countries displayed more severe outcomes, due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities. • Multivariate analysis demonstrated that the geographic area of residence, along with some clinical features (cardiac involvement, renal hypertension, lymphopenia, non-use of heparin prophylaxis) are strongly associated with unfavorable outcomes. [ABSTRACT FROM AUTHOR]

Background and Objectives: Early reports on COVID-19 infection suggested that the SARS-CoV-2 virus solely attacks respiratory tract cells. As the pandemic spread, it became clear that the infection is multiorganic. Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease strongly associated with insulin resistance and diabetes. The aim of this study was to assess a possible interplay between MAFLD and COVID-19 infection and its implication in COVID-19 outcome. Materials and Methods: A retrospective observational study, including 130 COVID-19 positive patients was conducted. MAFLD diagnosis was made based on the International Consensus criteria. Patients were divided into two groups, group A (MAFLD) and group B (nonMAFLD). Anthropometric and laboratory analysis were obtained. COVID-19 severity was assessed using the NEWS2 score. Disease outcome was threefold and regarded as discharged, patients who required mechanical ventilation (MV), and deceased patients. Results: MAFLD prevalence was 42%, 67% of patients were discharged, and 19% needed MV. Mortality rate was 14%. MAFLD patients were significantly younger (p < 0.001), and had higher body mass index (p < 0.05), respiratory rate (p < 0.05) and systolic blood pressure (p < 0.05) than nonMAFLD patients. Regarding metabolic syndrome and inflammatory markers: group A had significantly higher glycemia at admission (p = 0.008), lower HDL-c (p < 0.01), higher triglycerides (p < 0.01), CRP (p < 0.001), IL-6 (p < 0.05) and ferritin (p < 0.05) than group B. MAFLD was associated with more prevalent type 2 diabetes (p = 0.035) and hypertension (p < 0.05). MAFLD patients had a more severe disease course (NEWS2 score, 6.5 ± 0.5 vs. 3 ± 1.0, p < 0.05). MAFLD presence was associated with lower patient discharge (p < 0.01) and increased need for MV (p = 0.024). Multiple regression analysis showed that BMI (p = 0.045), IL-6 (p = 0.03), and MAFLD (p < 0.05) are significant independent risk factors for a poor COVID-19 outcome. Conclusions: The prevalence of MAFLD is relatively high. MAFLD patients had a more severe COVID-19 clinical course and worse disease outcome. Our results imply that early patient stratification and risk assessment are mandatory in order to avoid poor outcomes.

Reem Al Argan,1 Dania Alkhafaji,1 Abdulmohsen Al Elq,1 Waleed Albaker,1 Safi Alqatari,1 Alaa Alzaki,1 Abrar Alwaheed,1 Abir Al Said,1 Huda Bukhari,1 Sara Al Warthan,1 Mohammad Zeeshan,2 Fatimah AlRubaish,1 Zainab AlElq,1 Ahmed Alsahlawi,1 Mohannad Alalwan,1 Amani AlHwiesh,1 Fatimah I Alabdrabalnabi1 1Department of Internal Medicine, College of Medicine-Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Khobar, Eastern Province, Saudi Arabia; 2Department of Medical Education, College of Medicine, Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Khobar, Eastern Province, Saudi ArabiaCorrespondence: Reem Al ArganDepartment of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, King Fahd Hospital of the University, Khobar, Eastern Province, Saudi ArabiaTel +966 138957999 Extension 1842Email Rjalarqan@iau.edu.saPurpose: Diabetes mellitus (DM) has been reported to be associated with a worse outcome of COVID-19 infection. The evidence is scarce in the Middle East and Saudi Arabia. We aimed to evaluate the impact of diabetes mellitus and hyperglycemia in non-diabetic individuals on the severity and outcome of COVID-19 infection.Methods: This is a retrospective observational study, which included patients with confirmed COVID-19 infection [RT-PCR positive for SARS-CoV2] who were admitted to King Fahd Hospital of the University-Khobar-Eastern Province-Saudi Arabia from March to September 2020. Baseline demographic data, laboratory investigations, and markers of the severity of COVID-19 were analyzed. The collected data were categorized according to the Saudi Arabian Ministry of Health COVID-19 infection severity criteria. Patients were divided into three groups as follows: patients in Group 1 had pre-existing DM, patients in Group 2 did not have DM but were documented to have hyperglycemia at presentation, and patients in Group 3 were neither diabetics nor hyperglycemics at presentation and served as the control group. The severity and outcome of the control group were compared with the other two groups. The effect of risk factors on the severity and outcome of COVID-19 infection was studied in the DM group.Results: A total of 414 patients were included (70.5% males and 29.5% females). The mean age (SD) of patients was 52.3 (± 15.5) years. Compared to the control group, pre-existing DM was found to be significantly associated with severe (OR 3.61), critical disease (OR 4.32), intensive care unit (ICU) admission (OR 2.0), and death (OR 2.0) from COVID-19 infection. Hyperglycemia without known DM was also found to be associated with critical COVID-19 pneumonia (P 0.001), and had longer duration of hospitalization (P 0.014), higher ICU admission, mechanical ventilation, and death from COVID-19 infection (P < 0.0001).Conclusion: Diabetes mellitus and hyperglycemia at presentation, even in the absence of pre-existing DM, are independent risk factors for disease severity and worse outcome of COVID-19 infection. These patients should be identified and managed accordingly. The COVID-19 vaccination program should also target those populations to improve their outcomes.Keywords: COVID-19 infection, diabetes mellitus, hyperglycemia, disease severity, disease outcome, mortality

COVID-19 often manifests with different outcomes in different patients, highlighting the complexity of the host-pathogen interactions involved in manifestations of the disease at the molecular and cellular levels. In this paper, we propose a set of postulates and a framework for systematically understanding complex molecular host-pathogen interaction networks. Specifically, we first propose four host-pathogen interaction (HPI) postulates as the basis for understanding molecular and cellular host-pathogen interactions and their relations to disease outcomes. These four postulates cover the evolutionary dispositions involved in HPIs, the dynamic nature of HPI outcomes, roles that HPI components may occupy leading to such outcomes, and HPI checkpoints that are critical for specific disease outcomes. Based on these postulates, an HPI Postulate and Ontology (HPIPO) framework is proposed to apply interoperable ontologies to systematically model and represent various granular details and knowledge within the scope of the HPI postulates, in a way that will support AI-ready data standardization, sharing, integration, and analysis. As a demonstration, the HPI postulates and the HPIPO framework were applied to study COVID-19 with the Coronavirus Infectious Disease Ontology (CIDO), leading to a novel approach to rational design of drug/vaccine cocktails aimed at interrupting processes occurring at critical host-coronavirus interaction checkpoints. Furthermore, the host-coronavirus protein-protein interactions (PPIs) relevant to COVID-19 were predicted and evaluated based on prior knowledge of curated PPIs and domain-domain interactions, and how such studies can be further explored with the HPI postulates and the HPIPO framework is discussed.

Background and aim: Having weakness and lethargy and feeling the need for hospital emergency services is one of the most important reasons for patients to go to hospital emergency rooms. The aim of the present study was to investigate the relationship between morbidity and mortality of patients with weakness and lethargy. Method: The present study was conducted in an observational and prospective manner in the emergency department of Rasool Akram and Firouzgar hospitals. The patients were divided into 5 groups by the evaluation team in the emergency triage unit using the international valid triage tool "Emergency Severity Index (ESI)". The patients were followed up for 2 months after the time of discharge and the patient's condition was examined in terms of illness, health or death. Result: Between levels 1 and 2 (patients with high severity conditions) and 3 (patient needs two or more emergency facilities in case of no disturbance in vital signs), level 3 had the highest frequency of referrals (61.9%). 90.7% had an underlying disease and 66.1% of the patients were taking medication at the time of visit. 11% of patients died in the first visit. In the initial follow-up, 23.7% of people were still sick, 40.7% had recovered and 17.8% had died. Conclusion: According to results in the final follow-up, 3.9% of people were still sick; the rate of recovered patients in the final follow-up was 44.1% and the percentage of deaths in the final follow-up was 24.6%. The high mortality rate indicates that the patients' concern was not due to weakness and lethargy, but due to a dangerous underlying disease that forced them to go to the hospital. [ABSTRACT FROM AUTHOR]

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Abstract Background and Aim The number of elderly patients with ulcerative colitis (UC) is increasing worldwide. The clinical practice of associated treatment is still unclear. Therefore, we aimed to analyze clinical treatment realities and mortality in elderly and non‐elderly patients with UC. Methods We collected UC patients' data using the diagnosis procedure combination (DPC) database system and divided eligible patients into elderly (≥65 years) and non‐elderly (≤64 years) groups. We investigated and compared their therapeutic histories (medical treatments vs. surgery). Logistic regression analysis was conducted to identify clinical factors affecting surgery and in‐hospital death in each group. Results The rates of systemic steroid injection, molecular targeting drug usage, and surgery were not different between the two age groups. Meanwhile, the rate of in‐hospital death in elderly patients was higher than that in non‐elderly patients (2.7% vs. 0.19%, P

Objectives: Tuberculous meningitis (TBM) is the most severe form of infection caused by Mycobacterium tuberculosis (Mtb). Smurf1 represents a key component in anti-Mtb autophagic targeting in macrophages and in anti-TB host defense in vivo. We hypothesized that genetic variants in the Smurf1 gene region influence susceptibility to TBM. Methods: Using a case-control study design (235 TBM cases, 239 pulmonary TB cases and 478 healthy controls), we evaluated whether 8 haplotype-tagging single nucleotide polymorphisms (SNPs) in the Smurf1 gene are associated with the development of TBM. Results: Even with the most conservative correction, the polymorphism rs6956450 was associated with TBM under a dominant model (odds ratio [OR], 1.653; 95% confidence interval [CI], 1.192–2.294; P = 0.021), the CG haplotype consisting of rs3294 and rs6956450 was positively associated with TBM (P = 0.013) and another haplotype GC remained negatively associated with TBM in Tibetan subgroup (P < 0.001). No correlation was found between rs6956450 and TBM clinical characteristics or prognosis. Conclusions: These results firstly link the variants in the Smurf1 gene region with TBM risk, indicating an important role for Smurf1 in the immunopathogenesis of TBM. Future studies will dissect the mechanism, which may help identify targets or genetic markers to guide diagnosis or host-directed therapy in patients with TBM.

COVID-19 caused by SARS-CoV-2 infection is a highly contagious disease affecting both the higher and lower portions of the respiratory tract. This disease reached over 265 million people and has been responsible for over 5.25 million deaths worldwide. Skeletal muscle quality and total mass seem to be predictive of COVID-19 outcome. This systematic review aimed at providing a critical analysis of the studies published so far reporting on skeletal muscle mass in patients with COVID-19, with the intent of examining the eventual association between muscle status and disease severity. A meta-analysis was performed to evaluate whether skeletal muscle quantity, quality and function were related to disease severity. Systematic reviews and meta-analyses were conducted according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and reported according to the guidelines of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guide. From a total of 1,056 references found, 480 were selected after removing duplicates. Finally, only 7 met the specified inclusion criteria. The results of this meta-analysis showed that skeletal muscle quality, rather than quantity, was associated with COVID-19 severity, as confirmed by lower skeletal muscle density and lower handgrip strength in patients with severe disease. Muscle function assessment can thus be a valuable tool with prognostic value in COVID-19.

Amoebiasis, caused by the enteric parasite, Entamoeba histolytica , is one of the major food- and water-borne parasitic diseases in developing countries with improper sanitation and poor hygiene. Infection with E. histolytica has diverse disease outcomes, which are determined by the genetic diversity of the infecting strains. Comparative genetic analysis of infecting E. histolytica strains associated with differential disease outcomes from different geographical regions of the world is important to identify the specific genetic patterns of the pathogen that trigger certain disease outcomes of Amoebiasis. The strategy is able to elucidate the genealogical relation and population structure of infecting E. histolytica strains from different geographical regions. In the present study, we have performed a comparative genetic analysis of circulating E. histolytica strains identified from different parts of the world, including our study region, based on five tRNA-linked short tandem repeat (STR) loci (i.e., D-A , N K2 , R-R , S TGA -D and A-L) and evaluated their potential associations with differential disease outcomes of Amoebiasis. A number of regional-specific, emerging haplotypes of E. histolytica , significantly associated with specific disease outcomes have been identified. Haplotypes, which have a significant positive association with asymptomatic and amoebic liver abscess outcomes, showed a significant negative association with diarrheal outcome, or vice versa. Comparative multi-locus analysis revealed that E. histolytica isolates from our study region are phylogenetically segregated from the isolates of other geographical regions. This study provides a crucial overview of the population structure and emerging pattern of the enteric parasite, E. histolytica. [Display omitted] • Emerging haplotypes, significantly associated with disease outcomes were identified. • Haplotypes have positive association with LA, showed positive association with AS. • Phylogenetically segregated E. histolytica population was identified. [ABSTRACT FROM AUTHOR]