UBR-5 and UBE2D mediate timely exit from stem fate via destabilization of poly(A)-binding protein PABP-2 in cell state transition.

UBR5 E3 ligase has been associated with cancer susceptibility and neuronal integrity, with functions in chromatin regulation and proteostasis. However, the functions of ubr5 within animals remain unclear due to lethality in both mammals and flies when disrupted. Using Caenorhabditis elegans, we show that UBR-5 E3 ligase is required for timely exit of stem fate and complete transition into multiple cell type descendants in an ectodermal blast lineage. Animals lacking intact UBR-5 function simultaneously exhibit both stem fate and differentiated fate in the same descendant cells. A functional screen of UBR-5 physical interactors allowed us to identify the UBE2D2/3 E2 conjugase LET-70 working with UBR-5 to exit stem fate. Strikingly, we revealed that another UBR-5 physical interactor, namely the nuclear poly(A)-binding protein PABPN1 ortholog PABP-2, worked antagonistically to UBR-5 and LET-70. Lowering pabp-2 levels restored normal transition of cell state out of stemness and promoted normal cell fusion when either ubr-5 or let-70 UBE2D function was compromised. The UBR-5-LET-70 and PABP-2 switch works independently of the stem pool size determined by pluripotency factors like lin-28. UBR-5 limits PABP-2 protein and reverses the PABP-2-dependent gene expression program including developmental, proteostasis, and innate immunity genes. Loss of ubr-5 rescues the developmental stall when pabp-2 is compromised. Disruption of ubr-5 elevates PABP-2 levels and prolongs expression of ectodermal and muscle stem markers at the transition to adulthood. Additionally, ubr-5 mutants exhibit an extended period of motility during aging and suppress pabp-2-dependent early onset of immobility.

Individualised prediction of progression of solitary sub-solid pulmonary nodules based on CT semantic and clinical features: a 3-year follow-up study.

AIM: To develop and validate a progressive prediction model for estimating the time to progression (TTP) of sub-solid pulmonary nodules (SSNs). MATERIALS AND METHODS: A total of 126 cases who met inclusion and exclusion criteria were included in the study. The primary endpoint of the study was TTP of SSNs. Baseline characteristics were assessed in terms of clinical and CT semantic features. Kaplan-Meier analysis and Cox regression analysis were performed to determine the relationship between SSNs TTP and factors from the entire data set. The nomogram was constructed based on the result of multivariate analysis and internal validation was performed using the bootstrapping. The nomogram's performance was assessed with the C-index, calibration curves, and decision curve analysis. RESULTS: The median follow-up time of the population was 42.5 (21.5) months. On Kaplan-Meier analysis, patients with higher or positive values of the indices had higher cumulative progression rates (p<0.05). Multivariate Cox regression models identified diameter, consolidation tumour ratio (CTR), morphology, and vasodilation sign (VDS) as independent risk factors of TTP. These predictors were included in the final model to estimate individual probabilities of progression in the 3 years, which performed well in the discrimination (the C-index was 0.901 [95%CI: 0.830-0.981] and 0.875 [95%CI: 0.805-0.942] in the training and internally validation sets). CONCLUSION: The radiological semantic features nomogram is a promising and favourable prognostic biomarker for predicting progression and may aid in clinical risk stratification and decision-making for SSNs.

[The effect of glycopyrrolate on intestinal spasm and hemodynamics in painless colonoscopy].

Objective: To investigate the effects of glycopyrrolate on intestinal spasm and hemodynamics in painless colonoscopy. Methods: A total of 100 patients who were scheduled to undergo painless colonoscopy were selected as the study subjects and randomly divided into two groups by a computerized number method. Ten patients in both groups dropped out because of disruption of the study protocol, and 45 patients from each group were included in the final analysis. Before anesthesia induction, patients in group glycopyrrolate (group G) were injected with 0.2 mg glycopyrrolate, while those in congtrol group (group C) were injected with an equal amount of saline. The heart rate, systolic blood pressure, and diastolic blood pressure were recorded at T0 (baseline period), T1 (after anesthesia induction), T2 (colonoscopy over sigmoid colon), T3 (colonoscopy over the liver region), T4 (after the end of examination), and T5 (at the awakening phase), and the degree of intestinal spasm was assessed intraoperatively using the Likert's four-point scale. The numerical rating scale (NRS) was used to assess preoperative and postoperative pain. The incidence of adverse events was recorded. Results: The general data at baseline were not statistically different between the two groups (P>0.05). During the procedure, patients in group G had lower intraoperative intestinal spasm scores than those in group C (P=0.028). Intraoperative hypotension and bradycardia occurrence were lower in group G than in group C (P<0.05), and intraoperative norepinephrine use was also lower than in the group C (P=0.034). Postoperative visual analog scale pain scores were lower in group G (P=0.047), but patients who used glycopyrrolate had a higher proportion of dry mouth (P=0.035). Conclusion: During painless colonoscopy, preoperative administration of glycopyrrolate significantly improved intraoperative hemodynamic fluctuations, reduced the incidence of hypotension and bradycardia, and relieved postoperative pain. However, glycopyrrolate use resulted in the risk of dry mouth.

Neurodegeneration and humoral response proteins in cerebrospinal fluid associate with pediatric-onset multiple sclerosis and not monophasic demyelinating syndromes in childhood.

BACKGROUND: Pediatric-onset multiple sclerosis (POMS) represents the earliest stage of disease pathogenesis. Investigating the cerebrospinal fluid (CSF) proteome in POMS may provide novel insights into early MS processes. OBJECTIVE: To analyze CSF obtained from children at time of initial central nervous system (CNS) acquired demyelinating syndrome (ADS), to compare CSF proteome of those subsequently ascertained as having POMS versus monophasic acquired demyelinating syndrome (mADS). METHODS: Patients were selected from two prospective pediatric ADS studies. Liquid chromatography-mass spectrometry (LC-MS) was performed in a Dutch discovery cohort (POMS n = 28; mADS n = 39). Parallel reaction monitoring-mass spectrometry (PRM-MS) was performed on selected proteins more abundant in POMS in a combined Dutch and Canadian validation cohort (POMS n = 48; mADS n = 106). RESULTS: Discovery identified 5580 peptides belonging to 576 proteins; 58 proteins were differentially abundant with ⩾2 peptides between POMS and mADS, of which 28 more abundant in POMS. Fourteen had increased abundance in POMS with ⩾8 unique peptides. Five selected proteins were all confirmed within validation. Adjusted for age, 2 out of 5 proteins remained more abundant in POMS, that is, Carboxypeptidase E (CPE) and Semaphorin-7A (SEMA7A). CONCLUSION: This exploratory study identified several CSF proteins associated with POMS and not mADS, potentially reflecting neurodegeneration, compensatory neuroprotection, and humoral response in POMS. The proteins associated with POMS highly correlated with age at CSF sampling.

Gut microbiota analysis in pediatric-onset multiple sclerosis compared to pediatric monophasic demyelinating syndromes and pediatric controls.

BACKGROUND AND PURPOSE: Gut microbiota dysbiosis may lead to proinflammatory conditions contributing to multiple sclerosis (MS) etiology. Pediatric-onset MS patients are close to biological disease onset and less exposed to confounders. Therefore, this study investigated gut microbiota composition and functional pathways in pediatric-onset MS, compared to monophasic acquired demyelinating syndromes (mADS) and healthy controls (HCs). METHODS: Pediatric participants were selected from the Dutch national prospective cohort study including ADS patients and HCs <18 years old. Amplicon sequence variants (ASVs) were generated from sequencing the V3/4 regions of the 16S rRNA gene. Functional MetaCyc microbial pathways were predicted based on Enzyme Commission numbers. Gut microbiota composition (alpha/beta diversity and individual microbe abundance at ASV to phylum level) and predicted functional pathways were tested using nonparametric tests, permutational multivariate analysis of variance, and linear regression. RESULTS: Twenty-six pediatric-onset MS (24 with disease-modifying therapy [DMT]), 25 mADS, and 24 HC subjects were included. Alpha/beta diversity, abundance of individual resident microbes, and microbial functional features were not different between these participant groups. Body mass index (BMI) showed significant differences, with obese children having a lower alpha diversity (Chao1 Index p = 0.015, Shannon/Simpson Diversity Index p = 0.014/p = 0.023), divergent beta diversity (R2  = 3.7%, p = 0.013), and higher abundance of numerous individual resident microbes and functional microbial pathways. CONCLUSIONS: Previous results of gut microbiota composition and predicted functional features could not be validated in this Dutch pediatric-onset MS cohort using a more sensitive 16S pipeline, although it was limited by sample size and DMT use. Notably, several other host-related factors were found to associate with gut microbiota variation, especially BMI.

[Clinical features and related factors of invasive pulmonary aspergillosis in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To study the clinical features and related factors of invasive pulmonary aspergillosis (IPA) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: This retrospective study enrolled patients hospitalized for AECOPD in ten tertiary hospitals of China from September 2017 to July 2021. AECOPD patients with IPA were included as case group, AECOPD patients without IPA were randomly selected as control group from the same hospitals and same hospitalization period as the patients with IPA using the random function in the software of Microsoft Excel 2003, at a ratio of 2∶1. The clinical characteristics, treatment and outcome were compared between the two groups. Binary logistic regression model was used to analyze the factors associated with IPA in AECOPD patients. Results: A total of 14 007 inpatients with AECOPD were included in this study, and 300 patients were confirmed to have IPA, with an incidence rate of 2.14%. According to the above matching method, 600 AECOPD patients without aspergillus infection were enrolled as the control group. The age of the case group and the control group were (72.5±9.7) and (73.5±10.3) years old, with 78.0%(n=234) male and 76.8%(n=461) male, respectively. There were no significant differences in age and gender composition between the two groups (all P>0.05). The prognosis of case group was significantly worse than that of the control group, with longer hospital stay [M(Q1,Q3)], [14 (10-20) d vs 11 (8-15) d, P<0.001], higher ICU admission rate [16.3% (49 case) vs 10.0% (60 case), P=0.006], higher in-hospital mortality [4.0% (12 cases) vs 1.3% (8 cases), P=0.011], and higher hospitalization costs (28 000 ¥ vs 13 700 ¥, P<0.001). The smoking index of the case group and proportions of patients with diabetes mellitus, chronic pulmonary heart disease in the case group were significantly higher than those in control group (all P<0.05). In terms of clinical features, the proportions of patients with cough, expectoration, purulent sputum, hemoptysis and fever in the case group were higher than those in the control group, the serum albumin was significantly lower than that in the control group, and the proportions of patients with bronchiectasis and pulmonary bullae on imaging were significantly higher than those in the control group (all P<0.05). Diabetes (OR=1.559, 95%CI: 1.084-2.243), chronic pulmonary heart disease (OR=1.476, 95%CI: 1.075-2.028), bronchiectasis (OR=1.506, 95%CI: 1.092-2.078), pulmonary bullae (OR=1.988, 95%CI: 1.475-2.678) and serum albumin<35 g/L (OR=1.786, 95%CI: 1.325-2.406) were the related factors of IPA in patients with AECOPD. Conclusions: The incidence of IPA in AECOPD patients is relatively high and the prognosis of these patients is worse. Diabetes, chronic pulmonary heart disease, bronchiectasis, pulmonary bulla, hypoproteinemia are the related factors of IPA in patients with AECOPD.

Phenotypic homogeneity of emetic Bacillus cereus isolates in China.

Emetic Bacillus cereus strains produce a potent cereulide cytotoxin, which can cause acute and fatal cases of food poisoning. We isolated 18 emetic B. cereus strains from a food poisoning event, and from clinical and non-random food surveillance in China and phenotypic characteristics of haemolysis, starch hydrolysis, salicin fermentation, gelatin liquefaction, cytotoxicity, and susceptibility to antibiotics were assessed. All isolates were positive for haemolysis and gelatin liquefaction, and negative for starch hydrolysis and salicin fermentation. Their haemolytic potentials were intermediate to Bacillus anthracis and B. cereus ATCC 14579 (a non-emetic strain). All isolates were cytotoxic to CHO, Hep-2, and Vero cells, and were sensitive to ampicillin. The homogeneous phenotypes of emetic isolates from China are similar to the corresponding traits of European and Japanese isolates that have been characterized, suggesting highly similar phenotypes of emetic B. cereus worldwide.

[Risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: a multicenter retrospective study].

Objective: To investigate the risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: A total of 6 668 patients hospitalized for AECOPD in seven tertiary hospitals from September 2017 to January 2021 were consecutively included, and clinical data related to medical history, laboratory tests, treatment and prognosis were collected, and patients were divided into death group and survival group according to whether they died during hospitalization. After univariate analysis, multivariate logistic regression analysis was then performed to explore the independent risk factors related to in-hospital mortality. Results: Among 6 668 patients hospitalized for AECOPD, 128 patients experienced in-hospital death, with a mortality rate of 1.9%. The mean age of the death group was (81±9) years, which was significantly older than that of the survival group ((72±11) years P<0.001). The proportion of patients in the AECOPD in-hospital death group with a combination of prolonged bed rest, hypertension, myocardial infarction within 3 months, cardiac insufficiency, chronic pulmonary heart disease, pneumonia, type 2 diabetes, venous thromboembolism (VTE), and chronic renal insufficiency was also significantly higher than in the survival group (all P<0.05) The median length of stay in the in-hospital death group was 18 d, which was significantly longer than that in the survival group (9 d, P<0.001), and the proportion of patients admitted to the ICU, receiving invasive mechanical ventilation and non-invasive mechanical ventilation was also significantly higher than that in the survival group (all P<0.05). The white blood cell count, glutamic transaminase, blood creatinine, calcitoninogen, C-reactive protein, D-dimer, N-terminal B-type natriuretic and Pseudomonas aeruginosa infection rates were significantly higher than those in the survival group (all P<0.05). Multifactorial analysis showed that age>80 years (OR=3.82, 95%CI 2.36 to 6.18, P<0.001), prolonged bed rest (OR=2.95, 95%CI: 1.79 to 4.86, P<0.001), chronic pulmonary heart disease (OR=1.85, 95%CI: 1.14 to 3.00, P=0.012), and pneumonia (OR=2.75, 95%CI: 1.65 to 4.60, P<0.001), invasive mechanical ventilation (OR=7.33, 95%CI: 4.40 to 12.21, P<0.001), noninvasive mechanical ventilation (OR=3.73, 95%CI: 2.30 to 6.04, P<0.001), anemia (OR=2.03. 95%CI: 1.21 to 3.42, P=0.008), and calcitoninogen>0.5 ng/ml (OR=2.38, 95%CI: 1.41 to 4.02, P=0.001) were independent risk factors for in-hospital mortality in patients with AECOPD. Conclusion: Advanced age (>80 years), prolonged bed rest, chronic pulmonary heart disease, pneumonia, invasive mechanical ventilation, noninvasive mechanical ventilation, anemia, and calcitoninogen>0.5 ng/ml were independent risk factors for in-hospital mortality in patients hospitalized with AECOPD.

Safety and efficacy of taurine as an add-on treatment for tics in youngsters.

BACKGROUND AND PURPOSE: The pathophysiological model of tics generally describes disruption of γ-aminobutyric acid transmission, and taurine is found to be an agonist of γ-aminobutyric acid receptors. The study aimed to evaluate the safety and efficacy of taurine as an add-on treatment for tics. METHODS: Four hundred and four youngsters with tic disorders were randomly assigned to 12 weeks of either oral taurine or placebo. The Yale Global Tic Severity Scale was used to measure tic severity. The primary outcome measure was global severity scores reduced by more than 60% compared with baseline scores. RESULTS: Three hundred and eighty-two patients were successfully treated. At week 4, no significant differences were found in the treatment effect and the total occurrence of adverse drug reactions between the taurine and placebo groups. At week 12, the proportion of significant improvement in tics was significantly higher in the taurine group than the placebo group (53.4% with taurine versus 34.5% without taurine; relative risk 1.546; P < 0.001), and no group differences were found in the total occurrence of adverse drug reactions. CONCLUSIONS: Taurine is safe and effective for tics.

Interfacial mode coupling as the origin of the enhancement of T(c) in FeSe films on SrTiO3.

Films of iron selenide (FeSe) one unit cell thick grown on strontium titanate (SrTiO3 or STO) substrates have recently shown superconducting energy gaps opening at temperatures close to the boiling point of liquid nitrogen (77 kelvin), which is a record for the iron-based superconductors. The gap opening temperature usually sets the superconducting transition temperature Tc, as the gap signals the formation of Cooper pairs, the bound electron states responsible for superconductivity. To understand why Cooper pairs form at such high temperatures, we examine the role of the SrTiO3 substrate. Here we report high-resolution angle-resolved photoemission spectroscopy results that reveal an unexpected characteristic of the single-unit-cell FeSe/SrTiO3 system: shake-off bands suggesting the presence of bosonic modes, most probably oxygen optical phonons in SrTiO3 (refs 5, 6, 7), which couple to the FeSe electrons with only a small momentum transfer. Such interfacial coupling assists superconductivity in most channels, including those mediated by spin fluctuations. Our calculations suggest that this coupling is responsible for raising the superconducting gap opening temperature in single-unit-cell FeSe/SrTiO3.

The tumor suppressor NOR1 suppresses cell growth, invasiveness, and tumorigenicity in glioma.

Oxidored-nitro domain-containing protein 1 (NOR1) is a tumor suppressor downregulated in various human cancers, including nasopharyngeal carcinoma (NPC), lung cancer, and testicular cancer. NOR1 protein is highly expressed in the normal brain; however, its role in brain tumors remains unknown. In this study, we demonstrated that the NOR1 protein level was decreased in glioma tissue samples as compared to its normal counterpart. Exogenously expressed NOR1 protein in glioma U251 cells inhibits tumor cell proliferation, migration, and invasion. Re-expression of NOR1 induced cell cycle S to G2 phase arrest and suppressed its tumorigenicity in nude mice. Overexpression of NOR1 in U251 cells also led to a decrease of Ki67 expression in xenografts. Transcriptomic analysis revealed that NOR1 expression altered the expression of genes favored cell proliferation. Among the differentially expressed genes, FOXR2, a member of the FOX gene family, which promotes glioma progression, was decreased in NOR1 expressing cells. The downregulation of FOXR2 by NOR1 was validated in vitro and in vivo. Our findings suggest for the first time that NOR1 suppresses glioma progression via modulating the FOXR2 expression.

Ovarian teratoma-associated anti-NMDAR encephalitis in a 12-year-old girl.

The association of ovarian teratoma and anti-N-Methyl-Daspartate receptor (anti-NMDAR) is one of the most common autoimmune encephalitis syndromes and it is a serious and potentially fatal pathology that occurs in young women. This case report describes of a pediatric patient with anti-NMDAR encephalitis. A-12-year-old girl presented with abnormal behavior for one week came to Emergency Department of Sarawak General Hospital, Malaysia. She had psychotic spectrum symptoms including suicidal tendency. She was diagnosed with anti-NMDAR encephalitis as positive antibody was seen in her cerebrospinal fluid. She was treated with Injection Immunoglobulin. She turned out to have teratoma which was successfully removed later. Her progress was remarkable after the surgery with the Immunoglobulin. A multi-disciplinary team involving a psychiatrist, neurologist and gynaecologist liaised with intensivist to successfully manage the case and achieve the good outcome.

Momentum Dependence of the Nematic Order Parameter in Iron-Based Superconductors.

The momentum dependence of the nematic order parameter is an important ingredient in the microscopic description of iron-based high-temperature superconductors. While recent reports on FeSe indicate that the nematic order parameter changes sign between electron and hole bands, detailed knowledge is still missing for other compounds. Combining angle-resolved photoemission spectroscopy with uniaxial strain tuning, we measure the nematic band splitting in both FeSe and BaFe_{2}As_{2} without interference from either twinning or magnetic order. We find that the nematic order parameter exhibits the same momentum dependence in both compounds with a sign change between the Brillouin center and the corner. This suggests that the same microscopic mechanism drives the nematic order in spite of the very different phase diagrams.

High neurofilament levels are associated with clinically definite multiple sclerosis in children and adults with clinically isolated syndrome.

BACKGROUND: A promising biomarker for axonal damage early in the disease course of multiple sclerosis (MS) is neurofilament light chain (NfL). It is unknown whether NfL has the same predictive value for MS diagnosis in children as in adults. OBJECTIVE: To explore the predictive value of NfL levels in cerebrospinal fluid (CSF) for MS diagnosis in paediatric and adult clinically isolated syndrome (CIS) patients. METHODS: A total of 88 adult and 65 paediatric patients with a first attack of demyelination were included and followed (mean follow up-time in adults: 62.8 months (standard deviation (SD) ±38.7 months) and 43.8 months (SD ±27.1 months) in children). Thirty control patients were also included. Lumbar puncture was done within 6 months after onset of symptoms. NfL was determined in CSF using enzyme-linked immunosorbent assay (ELISA). COX regression analyses were used to calculate hazard ratios (HR) for clinically definite multiple sclerosis (CDMS) diagnosis. RESULTS: After adjustments for age, oligoclonal bands (OCB), and asymptomatic T2 lesions on baseline magnetic resonance imaging (MRI), increased NfL levels in both paediatric and adult CIS patients were associated with a shorter time to CDMS diagnosis (children HR = 3.7; p = 0.007, adults HR = 2.1; p = 0.032). For CIS patients with a future CDMS diagnosis, children showed higher NfL levels than adults (geometric mean 4888 vs 2156 pg/mL; p = 0.007). CONCLUSION: CSF NfL levels are associated with CDMS diagnosis in children and adults with CIS. This makes NfL a promising predictive marker for disease course with potential value in clinical practice.

Spectral Evidence for Emergent Order in Ba_{1-x}Na_{x}Fe_{2}As_{2}.

We report an angle-resolved photoemission spectroscopy study of the iron-based superconductor family, Ba_{1-x}Na_{x}Fe_{2}As_{2}. This system harbors the recently discovered double-Q magnetic order appearing in a reentrant C_{4} phase deep within the underdoped regime of the phase diagram that is otherwise dominated by the coupled nematic phase and collinear antiferromagnetic order. From a detailed temperature-dependence study, we identify the electronic response to the nematic phase in an orbital-dependent band shift that strictly follows the rotational symmetry of the lattice and disappears when the system restores C_{4} symmetry in the low temperature phase. In addition, we report the observation of a distinct electronic reconstruction that cannot be explained by the known electronic orders in the system.

Fatigue and physical functioning in children with multiple sclerosis and acute disseminated encephalomyelitis.

BACKGROUND AND OBJECTIVE: Fatigue and physical impairments are a major concern in children with multiple sclerosis (MS) and after acute disseminated encephalomyelitis (post-ADEM). We here aimed to evaluate the interaction between fatigue, exercise capacity, motor performance, neurological status, and quality of life (HRQoL). METHODS: In this cross-sectional study, data of 38 children (MS n = 22, post-ADEM n = 16), aged 4-17 years attending our national pediatric MS center, were studied. Fatigue was measured with the Pediatric Quality of Life Multidimensional Fatigue Scale, exercise capacity with the Bruce Protocol, motor performance with the Movement Assessment Battery for Children second edition, HRQoL with the Pediatric Quality of Life Questionnaire, and extent of disability with the Expanded Disability Status Scale (EDSS). RESULTS: Children with MS and post-ADEM experienced more fatigue ( p < 0.001), reduced exercise capacity ( p < 0.001), and impaired motor performance ( p < 0.001), despite low scores on the EDSS. Fatigue, but not the other parameters, was significantly correlated with HRQoL. Fatigue was not correlated with exercise capacity. CONCLUSION: We confirm the major impact of fatigue on quality of life in children with MS and post-ADEM. Fatigue was not explained by reduced exercise capacity or impaired motor performance. An important finding for clinical practice is that the low EDSS score did not reflect the poor physical functioning.

T-cell activation marker sCD27 is associated with clinically definite multiple sclerosis in childhood-acquired demyelinating syndromes.

BACKGROUND: Cerebrospinal fluid (CSF) levels of T-cell activation marker soluble CD27 (sCD27) are associated with subsequent disease activity after a first attack of suspected MS in adults. The predictive value for disease course in children with acquired demyelinating syndromes (ADS) is unknown. OBJECTIVES: To assess the predictive value of sCD27 levels for clinically definite multiple sclerosis (CDMS) diagnosis in childhood ADS. METHODS: Children <18 years with a first demyelinating event were prospectively included and followed. Soluble CD27 was determined in CSF using an enzyme-linked immunosorbent assay (ELISA). Cox regression analyses were used to calculate hazard ratios (HRs) for CDMS. RESULTS: A total of 94 ADS children were included (ADS with encephalopathy (ADS+) n = 33 and ADS without encephalopathy (ADS-) n = 61). Of the 61 ADS- children, 21 (48%) were diagnosed with CDMS during follow-up. At baseline, sCD27 levels were higher in patients with a future CDMS diagnosis ( n = 29) than in monophasic ADS+ ( n = 30), monophasic ADS- ( n = 28) and relapsing non-MS patients ( n = 7; p < 0.001). In ADS- patients, sCD27 was associated with CDMS (HR = 1.8 per 100 U/mL increase in sCD27 levels, p = 0.031), after adjustments for age, oligoclonal bands and the presence of dissemination in space on baseline magnetic resonance imaging (MRI). CONCLUSION: CSF sCD27 levels at first attack of demyelination were associated with CDMS diagnosis in children. This makes sCD27 a potential clinically relevant quantitative marker when performing routine CSF diagnostics.

[Individualized vancomycin dosing for a patient diagnosed as severe acute pancreatitis with concurrent extracorporeal membrane oxygenation and continuous veno-venous hemofiltration therapy: a case report].

Pharmacokinetic parameters can be significantly altered for acute kidney injury (AKI), extracorporeal membrane oxygenation (ECMO) and continuous veno-venous hemofiltration therapy (CVVH). Here we reported a case of individualized vancomycin dosing for a patient diagnosed as severe acute pancreatitis treated with concurrent ECMO and CVVH. A 65 kg 32-year-old woman was admitted to hospital presented with severe acute pancreatitis (SAP), respiratory failure, metabotropic acidosis and hyperkalemia. She was admitted to intensive care unit (ICU) on hospital day 1 and was initiated on CVVH. She progressed to multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) on ICU day 2, and veno-venous ECMO was instituted. Several catheters were inserted into the body to support ECMO, CVVH and pulse indicator continuous cardiac output (PiCCO), so vancomycin was prescribed empirically on ICU day 3 for prevention of catheter-related infection. Given the residual renal function and continuous hemofiltration intensity on day 3, vancomycin bolus of 1 000 mg was prescribed, followed by a maintenance dose of 500 mg every 8 hours. On ICU day 4, a vancomycin trough serum concentration of 14.1 mg/L was obtained before the fourth dose, which was within the target range of 10-20 mg/L. By ICU day 7, vancomycin dosage was elevated to 1.0 g every 12 hours because of aggravated infection and improved kidney function. On ICU day 14, a vancomycin trough serum concentration of 17 mg/L was obtained. Her white blood cell (WBC) and neutrophil percentage (Neut%) dropped to the normal level by ICU day 19. This vancomycin regimen was successful in providing a target attainment of trough serum concentration ranging from 10-20 mg/L quickly and in controlling infection-related symptoms and signs properly. With the help of this case report we want to call attention to the clinically significant alteration in vancomycin pharmacokinetics among critically ill patients. Individualized vancomycin dosing regimens and therapeutic drug monitoring are necessary for critically ill patients receiving CVVH and ECMO to ensure that the target serum vancomycin levels are reached to adequately treat the infection and avoid nephrotoxicity.

Mapping unmet supportive care needs, quality-of-life perceptions and current symptoms in cancer survivors across the Asia-Pacific region: results from the International STEP Study.

Background: To assess the supportive care needs, quality of life (QoL) and symptoms of patients with cancer after the end of first-line treatments and into survivorship in Asian countries using Australian data as benchmark. Patients and methods: A cross-sectional survey was carried out in Australia and eight high-income (HICs) and low-/middle-income (LMICs) Asian countries (China, Japan, Hong Kong SAR, South Korea, Myanmar, Thailand, India, Philippines) using validated scales (Cancer Survivors Unmet Needs scale), physical-symptom concerns (Cancer Survivors Survey of Needs subscale) and a single-item measure of global QoL perception. Results: Data were collected from 1873 patients. QoL was highest in Australia and all other countries had significantly lower QoL than Australia (all P < 0.001). One-quarter of the patients reported low QoL (scores 1-3/10). The most frequently reported symptoms were fatigue (66.6%), loss of strength (61.8%), pain (61.6%), sleep disturbance (60.1%), and weight changes (57.7%), with no difference in symptom experience between Australian data and all other countries, or between HICs and LMICs. Unmet needs of moderate/strong level were particularly high in all aspects assessed, particularly in the area of existential survivorship (psychosocial care) and receiving comprehensive cancer care. Australia and HICs were similar in terms of unmet needs (all low), but LMICs had a significantly higher number of needs both compared with Australia and HICs (all P < 0.001). Conclusion: Health care systems in Asian countries need to re-think and prioritize survivorship cancer care and put action plans in place to overcome some of the challenges surrounding the delivery of optimal supportive cancer care, use available resource-stratified guidelines for supportive care and test efficient and cost-effective models of survivorship care.