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789 versus 0.776 versus 0.760, respectively; P less then 0.001) and superior calibration. MELD-lactate had higher discrimination among hospitalizations with MELD ≤15 (AUC 0.763 versus 0.608 for MELD, global P = 0.01) and hospitalizations for infection (AUC 0.791 versus 0.674 for MELD, global P less then 0.001). We found a significant interaction between day 1 MELD-lactate and day 3 lactate clearance; heat maps were created as clinical tools to risk-stratify patients based on these clinical data. MELD-lactate had significantly superior performance in predicting in-hospital mortality among patients hospitalized for infection and/or with MELD ≤15 when compared with MELD or MELD-Na. Incorporating day 3 lactate clearance may further improve prognostication.
Central nervous system (CNS) malignancies are the most common solid tumors among children, and novel therapies are needed to help improve survival. Pomalidomide is an immunomodulatory agent that displays antiangiogenic and cytotoxic activity, making it an appropriate candidate to explore in pediatric CNS tumors.
A phase 1 first in pediatric trial of pomalidomide was conducted in children with recurrent, progressive, and refractory CNS tumors. The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) when given orally once daily for 21 consecutive days of a 28-day cycle. Once the MTD was established, 12 additional patients were enrolled on expansion cohorts based on age and steroid use.
Twenty-nine children were enrolled and 25 were evaluable for dose-limiting toxicity (DLT). The MTD was 2.6mg/m
(dose level 2). Four DLTs were observed in three patients at dose level 3 (3.4mg/m
) includeding grade 3 diarrhea, grade 3 thrombocytopenia, grade 3 lung infection, and grade 4 neutropenia. The most common adverse events were grade 1 and 2 myelosuppression. One patient with an oligodendroglioma had stable disease for nine cycles, and a second patient with an anaplastic pleomorphic xanthoastrocytoma achieved a sustained partial response. Immunologic analyses suggested that pomalidomide triggers immunomodulation.
The MTD of pomalidomide is 2.6mg/m
. It was well tolerated, and immune correlates showed a serum immune response. These data led to an industry-sponsored phase 2 trial of pomalidomide monotherapy in children with recurrent brain tumors (NCT03257631).
The MTD of pomalidomide is 2.6 mg/m2 . It was well tolerated, and immune correlates showed a serum immune response. These data led to an industry-sponsored phase 2 trial of pomalidomide monotherapy in children with recurrent brain tumors (NCT03257631).The pandemic is creating unprecedented demand for mental health support for young people. While schools often facilitate mental health support for their students, the demands for online teaching and the uncertainty created by the pandemic make traditional delivery of support through schools challenging. Technology provides a potential way forward. We have developed a digital ecosystem, HABITS, that can be integrated into school and healthcare systems. This has allowed us to deploy specific evidence-based interventions directly, and through schools, to students and to parents in New Zealand during the current pandemic. Chatbot architecture is particularly suited to rapid iteration to provide specific information while apps can provide more generalised support. While technology can provide some solutions, it is important to be aware of the potential to increase current inequities, with those facing the greatest challenges to health and well-being, also least able to afford the resources to access digital interventions. Development of an integrated and equitable digital system will take time and collaboration.We present a method to map fluorescence resonance energy transfer (FRET) parameters of a bifunctional photodynamic therapy agent, (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a)-cyanine dye (HPPH-CD) conjugate, which consists of a photosensitizer (HPPH) and a fluorescent agent CD. We utilized time-domain fluorescence diffuse optical tomography, the normalized Born ratio model in the Fourier-domain, and an iterative algorithm to map depth-resolved spatial heterogeneities of FRET parameters. Our results exhibited depth-resolved changes of fluorophore's lifetime and the distance maps due to FRET between HPPH and CD. Our model suggests a potential approach of using FRET parameters to monitor efficacies of multifunctional photodynamic therapy agents in deep tissue.
Erdheim Chester disease (ECD) is very rare in pediatrics with no standard treatment guidelines. Here we present the case of a pediatric ECD patient who was cured with a Langerhan cell histiocytosis (LCH) directed chemotherapy protocol.
The aim of the report was to publish this rare presentation of ECD in pediatrics and highlight the complete response obtained to treatment.
The details of the patient were extracted by a retrospective review of her clinical records.
An 11 years old girl presented with fever and bone pain. On investigating she had multiple lytic bony lesions scattered throughout her skeleton. A biopsy from one of the bone lesions confirmed the diagnosis to be ECD. ECD is very rare in pediatrics and this case adds to the existing list of 11 previously reported ones. Also, worth mention is the fact that the child presented with isolated skeletal involvement in form of multiple osteolytic lesions. The child was started on the LCH-III protocol on which she achieved a cure.
Lytic bone lesions in a child may be present in ECD. A subset of ECD may have good response to LCH like chemotherapy.
Lytic bone lesions in a child may be present in ECD. A subset of ECD may have good response to LCH like chemotherapy.A gram-negative plant-pathogenic bacterium Ralstonia solanacearum strain OE1-1 produces and extracellularly secretes methyl 3-hydroxymyristate (3-OH MAME), and senses the chemical as a quorum-sensing (QS) signal, activating QS. During QS a functional global transcriptional regulator PhcA, through the 3-OH MAME-dependent two-component system, induces the production of virulence factors including a major extracellular polysaccharide EPS I and ralfuranone. To elucidate the mechanisms of phcA regulation underlying the QS system, among Tn5-mutants from the strain OE1-1, we identified a mutant of RSc1351 gene (phcK), encoding a putative sensor histidine kinase, that exhibited significantly decreased QS-dependent cell aggregation. We generated a phcK-deletion mutant (ΔphcK) that produced significantly less EPS I and ralfuranone than the wild-type strain OE1-1. Quantitative reverse transcription PCR assays showed that the phcA expression level was significantly down-regulated in the ΔphcK mutant but not in other QS mutants. The transcriptome data generated with RNA sequencing technology revealed that the expression levels of 88.2% of the PhcA-positively regulated genes were down-regulated in the ΔphcK mutant, whereas the expression levels of 85.9% of the PhcA-negatively regulated genes were up-regulated. Additionally, the native phcK-expressing complemented ΔphcK strain and the ΔphcK mutant transformed with phcA controlled by a constitutive promoter recovered their cell aggregation phenotypes. Considered together, the results of this study indicate that phcK is required for full phcA expression, thereby driving the QS circuit of R. solanacearum strain OE1-1. This is the first report of the phcA transcriptional regulation of R. solanacearum.Scars are often considered to be skin problems that affect beauty. The tension acting on the edge of the wound is the main factor causing the scar hyperplasia. At present, the clinical use of botulinum toxin A (BTX-A) around the wound to cause transient muscle paralysis reduce the muscle movement around the wound and wound tension to prevent scar hyperplasia during wound healing. But the use of BTX-A to prevent scarring requires the use of a syringe. The syringe can cause trauma and pain when it pricks the skin for BTX-A injection. The conotoxin which is secreted by the poison glands on the inside of the venom tube and capsule of the snail provides a simple and effective way to prevent skin scar hyperplasia. We reviewed the classification of conotoxin, the conotoxin's mechanism of preventing scar hyperplasia, and the research direction of conotoxin in the future and provided reference for promoting the application of conotoxin in preventing skin scar hyperplasia.
Proctology is one of the surgical specialties that has suffered the most during COVID-19 pandemic. Using a cross-sectional non-incentivised World Wide Web survey, we aimed to snapshot the current status of proctological practice in six world regions.
Surgeons affiliated to renowned scientific societies with an interest in coloproctology were invited to join the survey. learn more Members of the ProctoLock Working Group enhanced recruitment by direct invitation. The predictive power of respondents' and hospitals' demographics on the change of status of surgical and outpatient activities was calculated.
Respondents (n=1050) were mostly men (79%), with a mean age of 46.9years, at consultant level (79%), practising in academic hospitals (53%) offering a dedicated proctology service (68%). A total of 119 (11%) tested positive for SARS-CoV-2. The majority (54%) came from Europe. Participants from Asia reported a higher proportion of unaltered practice (17%), while those from Europe had the highest proportion of fully stopped practice (20%). The likelihood of ongoing surgical practice was higher in men (OR 1.54, 95% CI 1.13-2.09; P=0.006), in those reporting readily availability of personal protective equipment (PPE) (OR 1.40, 1.08-1.42; P=0.012) and in centres that were partially or not at all involved in COVID-19 care (OR 2.95, 2.14-4.09; P<0.001). This chance decreased by 2% per year of respondent's age (P=0.001).
Several factors including different screening policies and resource capacity affected the current status of proctological practice. This information may help health authorities to formulate effective preventive strategies to limit curtailment of care of these patients during the pandemic.
Several factors including different screening policies and resource capacity affected the current status of proctological practice. This information may help health authorities to formulate effective preventive strategies to limit curtailment of care of these patients during the pandemic.
Intrafraction imaging is an Elekta feature that enables cone beam computed tomography (CBCT) acquisition simultaneously with treatment arc delivery. It has facilitated the introduction of breath-hold (BH) gated stereotactic body radiation therapy (SBRT) by enabling visualisation of tumour and organs at risk during treatment. The aims of this study were to assess BH reproducibility and use intrafraction CBCT (IF-CBCT) to quantify any variation in diaphragm position (diaphragmatic feathering) during the multiple BHs performed during each arc.
IF-CBCTs for consecutive liver SBRT patients where BH was achieved using the Elekta Active Breathing Control (ABC) system were retrospectively evaluated. Average intrafraction couch shifts for deep-inspiration BH (DIBH) or end-expiration BH (EEBH) were recorded as an indication of reproducibility. Diaphragmatic feathering was quantified by measuring the difference between the most superior and inferior visible edges of the diaphragm on IF-CBCTs.
A total of 212 images from 30 patients were reviewed.
