Diagnosing tuberculosis (TB) in children is challenging due to paucibacillary disease, and lack of ability for microbiologic confirmation. Hence, we measured the plasma chemokines as biomarkers for ...diagnosis of pediatric tuberculosis. We conducted a prospective case control study using children with confirmed, unconfirmed and unlikely TB. Multiplex assay was performed to examine the plasma CC and CXC levels of chemokines. Baseline levels of CCL1, CCL3, CXCL1, CXCL2 and CXCL10 were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics curve analysis revealed that CCL1, CXCL1 and CXCL10 could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 80%. In addition, combiROC exhibited more than 90% sensitivity and specificity in distinguishing confirmed and unconfirmed TB from unlikely TB. Finally, classification and regression tree models also offered more than 90% sensitivity and specificity for CCL1 with a cutoff value of 28 pg/ml, which clearly classify active TB from unlikely TB. The levels of CCL1, CXCL1, CXCL2 and CXCL10 exhibited a significant reduction following anti-TB treatment. Thus, a baseline chemokine signature of CCL1/CXCL1/CXCL10 could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
To describe the clinical presentation, phenotype and outcome of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) from a tertiary ...care center in southern India.
Methods
257 children fulfilling the inclusion criteria of MIS-C were prospectively enrolled from June, 2020 to March, 2022.
Results
Median (range) age at presentation was 6 year (35 day to 12 years). Presenting features were fever (98%), vomiting (75.8%), red eyes (63%), rashes (49%), pain abdomen (49%), shock (45.9%), lymphopenia (73%, thrombocytopenia (58.3%) and anemia (45%). 103 (39.7%) children required intensive care admission. Shock phenotype, Kawasaki-like phenotype and no specific phenotype were diagnosed in 45.9%, 44.4%, and 36.6% children, respectively. Left ventricular dysfunction (30.3%), acute kidney injury (13%), acute liver failure (17.4%), and hemophagolymphohistiocytosis (HLH) (13.6%) were the major system involvement in MIS-C. Mitral regurgitation (
P
=0.029), hyperechogenic coronaries (
P
=0.006), left ventricular dysfunction (
P
=0.001) and low ejection fraction (
P
=0.007) were significantly associated with shock. Overall mortality was 11.7%.
Conclusions
Kawasaki-like and shock-like presentation were common in MIS-C. Coronary abnormalities were seen in 118 (45.9%) children. Children with acute kidney injury, HLH, need for mechanical ventilation, and echocardiogram evidence of mitral regurgitation in MIS-C have a poor outcome.
Objectives
To know the clinical presentation and outcome of children with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV- 2 (PIMS-TS) at a pediatric tertiary care ...center in Chennai.
Methods
Clinical and biochemical parameters of 65 children with PIMS-TS treated between July and October 2020 were studied. All children had their COVID RT-PCR and IgG COVID antibodies tests done.
Results
Mean age of the study group was 5.65 ± 3.68 y. Fever with red eyes, rash, vomiting, abdominal pain, and shock were common presenting features. Sixty percent of the study group had Kawasaki/incomplete Kawasaki features. Sixty-seven percent of the study group had coronary dilatation, 41% presented with shock, and 25% had left ventricular dysfunction. Coronary aneurysms were documented in 58% of the study group (
z
score more than 2.5). Respiratory presentation with pneumonia was seen in 10%. Four children presented with acute abdomen. Acute kidney injury, acute liver failure, hemolysis, pancytopenia, macrophage activation syndrome, encephalopathy, and multiorgan dysfunction syndrome (MODS) were other features. Forty-three percent required noninvasive oxygen support and 15.4% required mechanical ventilation. Intravenous immunoglobulin (73.8%) and methylprednisolone (49.8%) were used for therapy. Mortality in the study was 6%, which was due to MODS.
Conclusions
Acute febrile illness with mucocutaneous and gastrointestinal manifestations should have PIMS-TS as a possible differential diagnosis and needs evaluation with inflammatory markers and SARS-CoV-2 antibodies.
Pediatric TB poses challenge in diagnosis due to the paucibacillary nature of the disease. We conducted a prospective diagnostic study to identify immune biomarkers of pediatric TB and controls ...(discovery cohort) and obtained a separate "validation" cohort of confirmed cases of pediatric TB and controls. Multiplex ELISA was performed to examine the plasma levels of cytokines. Discovery and validation cohorts revealed that baseline plasma levels of IFNγ, TNFα, IL-2, and IL-17A were significantly higher in active TB (confirmed TB and unconfirmed TB) in comparison to unlikely TB children. Receiver operating characteristics (ROC) curve analysis revealed that IFNγ, IL-2, TNFα, and IL-17A (in the discovery cohort) and TNFα and IL-17A (in the validation cohort) could act as biomarkers distinguishing confirmed or unconfirmed TB from unlikely TB with the sensitivity and specificity of more than 90%. In the discovery cohort, cytokines levels were significantly diminished following anti-tuberculosis treatment. In both the cohorts, combiROC models offered 100% sensitivity and 98% to 100% specificity for a three-cytokine signature of TNFα, IL-2, and IL-17A, which can distinguish confirmed or unconfirmed TB children from unlikely TB. Thus, a baseline cytokine signature of TNFα, IL-2, and IL-17A could serve as an accurate biomarker for the diagnosis of pediatric tuberculosis.
The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to ...prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Children living with human immunodeficiency virus (HIV, CLWH) are at high risk of tuberculosis (TB) and face poor outcomes, despite antiretroviral therapy (ART). We evaluated ...outcomes in CLWH and children not living with HIV treated for nonsevere TB in the SHINE trial. Methods SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, nonsevere TB who were randomized to receive 4 versus 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CLWH. Results Of 1204 children enrolled, 127 (11%) were CLWH, of similar age (median, 3.6 years; interquartile range, 1.2, 10.3 versus 3.5 years; 1.5, 6.9; P = .07) but more underweight (weight-for-age z score, −2.3; (3.3, −0.8 versus −1.0; −1.8, −0.2; P < .01) and anemic (hemoglobin, 9.5 g/dL; 8.7, 10.9 versus 11.5 g/dL; 10.4, 12.3; P < .01) compared with children not living with HIV. A total of 68 (54%) CLWH were ART-naive; baseline median CD4 count was 719 cells/mm3 (241–1134), and CD4% was 16% (10–26). CLWH were more likely to be hospitalized (adjusted odds ratio, 2.4; 1.3–4.6) and to die (adjusted hazard ratio aHR, 2.6; 95% confidence interval CI, 1.2 to 5.8). HIV status, age <3 years (aHR, 6.3; 1.5, 27.3), malnutrition (aHR, 6.2; 2.4, 15.9), and hemoglobin <7 g/dL (aHR, 3.8; 1.3,11.5) independently predicted mortality. Among children with available viral load (VL), 45% and 61% CLWH had VL <1000 copies/mL at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 versus 6 months) on TB treatment outcomes by HIV status (P for interaction = 0.42). Conclusions We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CLWH treated for nonsevere TB. Irrespective of TB treatment duration, CLWH had higher rates of mortality and hospitalization than their counterparts not living with HIV. Clinical Trials Registration. ISRCTN63579542.
Background: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children in both the community and hospital setting. Ongoing surveillance of the clinical ...and molecular epidemiology of RSV genotypes is important to characterize prevalent and emerging genotypes that may have impact on vaccine development. Objective: To assess the epidemiology of RSV infection in children <5 years of age in a tertiary care hospital. Materials and Methods: Children <5 years of age hospitalized with severe community-acquired pneumonia (CAP) were included in the study. Nasopharyngeal aspirate was taken for RSV reverse-transcriptase polymerase chain reaction. Results: A total of 100 children were recruited in the study. clinicoepidemiological epidemiological and radiological features were analyzed. The prevalence of RSV infection in children <60 months of age admitted with the features of severe pneumonia in our study was 30% with almost equal proportion of RSV A and B groups. Underlying congenital heart disease and family history of asthma were identified as significant risk factors. There were no significant clinical and radiological features to distinguish RSV from non-RSV disease. Conclusions: This study highlights the relevance of RSV infection in hospitalized cases of CAP in our region. Our findings warrant the conduct of further investigations which can help design strategies for controlling the disease. If RT-PCR could be used in children with severe pneumonia who are hospitalized, an accurate diagnosis of RSV bronchiolitis can be made in high percentage of children.
LiteSteel (LSB) beams are made of two rectangular hollow flanges and a slender web. Although the flexural capacity and bending stiffness are enhanced due to hollow flanges, they are vulnerable to the ...web crippling failure under concentrated loads and reactions due to high web slenderness values. In current steel buildings, cold-formed steel sections with web holes have been used to accommodate service ducts in floor systems. These LiteSteel beams (LSBs) are innovative new sections, hence current web crippling equations cannot be used to predict the web crippling capacities of them. Keerthan et al. (2014, 2016) and Steau et al. (2015) proposed coefficients to the unified web crippling equation which is available in Australian/New Zealand standard (AS/NZS 4600) and North American Specification (AISI S100) for unfastened and fastened supports, respectively for LSB sections without web holes under four load cases based on their experimental studies. However web crippling behaviour of these sections with web holes is still unknown under all four load cases. In past studies, the web holes are classified into two groups such as centred beneath and offset web holes to investigate their effect on the web crippling behaviour. This study investigates web crippling behaviour of LiteSteel beams with centred beneath and offset circular web holes with unfastened supports under End-Two-Flange load case (ETF) using finite element analysis in ANSYS. Accurate validations have been performed for five different web crippling datasets, and the parametric study was conducted using validated FE models. Web crippling equations were proposed for LiteSteel beams with centred beneath and offset web holes and without web holes based on 1067 FE model values.
Over the last decade, interest in the utilization of solar energy for photocatalysis treatment processes has taken centre-stage. Researchers had focused on doping TiO
2
with SiO
2
to obtain an ...efficient degradation rate of various types of target pollutants both under UV and visible-light irradiation. In order to further improve this degradation effect, some researchers resorted to incorporate plasmonic metal nanoparticles such as silver and gold into the combined TiO
2
-SiO
2
to fully optimize the TiO
2
-SiO
2
’s potential in the visible-light region. This article focuses on the challenges in utilizing TiO
2
in the visible-light region, the contribution of SiO
2
in enhancing photocatalytic activities of the TiO
2
-SiO
2
photocatalyst, and the ability of plasmonic metal nanoparticles (Ag and Au) to edge the TiO
2
-SiO
2
photocatalyst toward an efficient solar photocatalyst.
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