Background In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). MethodsWe did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome). Findings 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0•85-1•22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8-14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 µg/L to 1659 µg/L), and ferritin (1042 μg/L to 757 μg/L), whereas the lymphocyte count increased to more than 1•0 × 10⁹ cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died.Interpretation During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown.Funding None.

Measurements and Main Results: De-identified data collected as part of routine clinical care was analysed. All children were diagnosed and staged for AKI based on the level of serum creatinine above the upper limit of reference interval (ULRI) values according to published guidance. Severe AKI was defined as stage 2/3 AKI. Uni-and multi-variable analyses were performed to study the association between demographic data, clinical features, markers of inflammation and cardiac injury, and severe AKI. Over the study period, 116 patients with PIMS-TS were admitted to 15 UK PICUs. Any-stage AKI occurred in 48/116 patients (41.4%), and severe AKI in 32/116 (27.6%) patients, which was mostly evident at admission (24/32, 75%). In univariable analysis, body mass index, hyperferritinemia, high C-reactive protein (CRP), Pediatric Index of Mortality 3 (PIM3) score, vasoactive medication and invasive mechanical ventilation (IMV) were associated with severe AKI. In multivariable logistic regression, hyperferritinemia was associated with severe AKI (compared to non-severe AKI, adjusted odds ratio 1.04, 95% CI 1.01-1.08, p=0.04). Severe AKI was associated with longer PICU stay (median 5 days [IQR 4,7] vs 3 days [IQR 1.5,5], p<0.001) and increased duration of IMV (median 4 days [IQR 2,6] vs 2 days [IQR 1,3], p=0.04). Conclusions: Severe AKI occurred in just over a quarter of children admitted to UK PICUs with PIMS-TS. Hyperferritinemia was significantly associated with severe AKI. Severe AKI was associated with increased duration of stay and ventilation. Although short-term outcomes for AKI in PIMS-TS appear good, long-term outcomes are unknown.

Induction of nuclear factor kappa B (NF-κB)-mediated gene expression has been implicated in the pathogenesis of alcoholic liver disease through enhanced production of reactive oxygen species and pro-inflammatory mediators. The present study was carried out to investigate the role of catechin as a chain breaking inhibitor against experimental alcoholic liver injury. Rats were administered 35% v/v ethanol orally at a dose of 10 g/Kg/day for two weeks, followed by 14 g/Kg/day for 10 weeks. Catechin (50 mg/Kg) was co-supplemented after 4 weeks of alcohol treatment till the end of the dosing period. Following chronic alcohol exposure, rats developed endotoxemia and severe pathological changes in the liver such as pronounced fatty change, vacuolar degeneration and inflammation. These changes were accompanied by activation of NF-κB and induction of inflammatory and cytotoxic mediators leading to increased level of tumor necrosis factor-alpha, enhanced formation of malondialdehyde in the liver followed by drastic alterations in the hepatic antioxidant defense systems. Additionally, nitrite levels and lactate dehydrogenase activities were also significantly elevated on chronic alcohol consumption. Alcohol exposure also increased the number of micronucleated cells indicating that alcohol abuse may again be associated with the nuclear changes. Supplementation with catechin ameliorated the alcohol-induced liver injury by downregulating the endotoxin-mediated activation of initial signalling molecule NF-κB and further going downstream the signalling cascade including tumor necrosis factor-alpha, nitric oxide and reactive oxygen species and by enhancing the antioxidant profile. These observations correlated well with the histological findings. Moreover, a remarkable decrease in the percentage of micronucleated cells was observed with catechin supplementation indicating an apparent protection against alcohol-induced toxicity. These findings suggest that catechin may alleviate experimental alcoholic liver disease by suppressing induction of NF-κB, a key component of signalling pathway, thus forming a pharmacological basis for designing novel therapeutic agents against alcohol induced endotoxin-mediated liver injury.

Targeting altered pathways during initial stage of hepatocellular carcinoma (HCC) development is viewed as an effective and promising strategy to control this disease. Present study investigated the potential effect of lycopene-enriched tomato extract (LycT) on hypoxia-induced factor (HIF)-1α, HOX, VEGF, CD31, matrix metalloproteinase (MMP)-2, MMP-9, and alpha fetoprotein (AFP)expression during initial stages of N-nitrosodiethylamine (NDEA) induced HCC. Female Balb/c mice (8-10 wk) were assigned to 4 groups: control, NDEA (200 mg NDEA i.p./kg body weight, cumulative), LycT (5 mg lycopene orally/kg body weight; 3 times a week), and LycT + NDEA. LycT treatment began 2 wk before NDEA administration and continued until the end of the 10 wk study. The onset of HCC by NDEA was associated with significant alteration in serum biochemical markers [alanine transaminases (ALT), aspartate transaminases (AST), and alkaline phosphatases (ALP), lactate dehydrogenase (LDH), urea, A/G ratio, and bilirubin] and in liver histopathology. LycT treatment significantly reduced the levels of these markers. LycT treatment to NDEA mice also led to significant reduction in protein levels of AFP, HIF-1α, VEGF, CD31, MMP-2, and MMP-9 in comparison with NDEA group alone. These parameters are important biomarkers of hypoxia, angiogenesis, and metastasis, which reflect the advanced disease stage. The study provides evidence that prophylactic dietary supplementation with LycT may counteract HCC progression and/or protect against disease onset.

A 95% ethanol extract from whole aerial parts of Euphorbia hirta (EH A001) showed antihistaminic, antiinflammatory and immunosuppressive properties in various animal models. EH A001 inhibited rat peritoneal mast cell degranulation triggered by compound 48/80. It significantly inhibited dextran-induced rat paw edema. EH A001 prevented eosinophil accumulation and eosinophil peroxidase activity and reduced the protein content in bronchoalveolar lavage fluid (BALF) in a 'mild' model of asthma. Moreover, the CD4/CD8 ratio in peripheral blood was suppressed. EH A001 attenuated the release of interleukin-4 (IL-4) and augmented interferon-gamma (IFN-gamma) in ovalbumin-sensitized mouse splenocytes. The results were compared with the effects of known compounds, ketotifen, cetirizine and cyclophosphamide. These findings demonstrated that Euphorbia hirta possessed significant activity to prevent early and late phase allergic reactions.

introduction: The aim of the present study was to compare the therapeutic efficacy of 153 Lu-EDTMP in pain palliation in cancer patients with skeletal metastases. Materials and methods:Thirty patients (25 M:5 F, mean age: 66.0 ± 14.7 years) of breast/prostate cancer with documented skeletal metastases were recruited prospectively. Twenty patients were considered randomly for treatment with Lu-EDTMP was considered as reference images. All the serial images were used for patients' dosimetry analysis by using organ level internal dosimetry assessment algorithm. Reduction in pain scoring was assessed clinically over 8 weeks by using appropriate WHO criteria and correlated with the absorbed dose to the metastatic sites.results: A total of 86 metastatic lesions clearly visualized on post-therapy serial images (matching on bone scans) were evaluated for absorbed dose calculations. Both 153 Sm-EDTMP and 177 Lu-EDTMP delivered similar absorbed dose to the metastatic sites, i.e., 6.22 ± 4.21 and 6.92 ± 3.92 mSv/MBq, respectively. The mean absorbed doses to various other organs were found to be comparable and within the safe limits. A complete response (CR) for each radionuclide was evaluated as 80.0%. No significant alternation in blood parameters and no untoward reaction were observed. However, a mild to severe toxicity was observed in two patients (1 each with 153

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The use of botanicals for maintaining good health and preventing diseases is undisputed. The claimed health benefits of natural health products and herbal medicines are based on traditional claims, positive results obtained in preclinical studies and early phase clinical trials that are not backed by safety and efficacy evidences approved by regulatory agencies. Although, the popularity of botanicals is growing, health care practitioners of modern medicine seldom recommend their use because of ill equipped database of their safety and potency. This review discusses problems that preclude botanicals from integrating into the mainstream contemporary therapeutics and cues that provide impetus for their realisation.