hy Persistent Hyponatremia in an Elderly Patient By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Hyponatremiahyposmolarreset osmostatsyndrome of inappropriate antidiuresiselderly Full Article
hy Commentary on Persistent Hyponatremia in an Elderly Patient By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Lai et al. report the case of an elderly gentleman who presented with resolving neurologic findings from a transient ischemic attack and who was found to have hyponatremia with a serum sodium concentration of 123 mmol/L. Hypoosmolality was confirmed, and a diluting defect identified with a urine osmolality that ranged between 167 and 285 mOsm/kg. As the urine osmolality rose to > 400 mOsm/kg with water deprivation, a diagnosis of syndrome of inappropriate antidiuresis (SIAD) from reset osmostat was entertained. Full Article
hy Commentary on Persistent Hyponatremia in an Elderly Patient By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Hyponatremia, the most common electrolyte disorder, is present in 2%–4% of ambulatory patients and up to 22% of geriatric inpatients (1). Clinicians classify hyponatremia into three main categories: hypovolemic (decreased intravascular volume from salt and water loss with inadequate replacement), euvolemic (normal intravascular volume, but increased water dilutes sodium), and hypervolemic (total body water is increased, usually causing edema, while intravascular volume is often decreased). Less frequent causes are pseudohyponatremia (due to decreased water in a fixed volume of plasma, usually due to increased lipids or protein) and water shifting due to increased osmolality (most commonly due to glucose). While the most extreme examples of hypovolemic and hypervolemic states can be determined by physical examination, in many cases the patient is euvolemic clinically. Full Article
hy Metabolic Acidosis and Hypoglycemia in a Child with Leigh-Like Phenotype By academic.oup.com Published On :: Thu, 30 Apr 2020 00:00:00 GMT Full Article
hy Design of the {beta}3-Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure Trial By www.basictranslational.onlinejacc.org Published On :: 2020-04-27T11:00:20-07:00 Combined pre-and post-capillary hypertension (CpcPH) is a relatively common complication of heart failure (HF) associated with a poor prognosis. Currently, there is no specific therapy approved for this entity. Recently, treatment with beta-3 adrenergic receptor (β3AR) agonists was able to improve pulmonary hemodynamics and right ventricular (RV) performance in a translational, large animal model of chronic PH. The authors present the design of a phase II randomized clinical trial that tests the benefits of mirabegron (a clinically available β3AR agonist) in patients with CpcPH due to HF. The effect of β3AR treatment will be evaluated on pulmonary hemodynamics, as well as clinical, biochemical, and advanced cardiac imaging parameters. (Beta3 Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure [SPHERE-HF]; NCT02775539) Full Article
hy Overdiagnosis of lung cancer with low-dose computed tomography screening: meta-analysis of the randomised clinical trials By breathe.ersjournals.com Published On :: 2020-03-18T06:44:39-07:00 In low-dose computed tomography (LDCT) screening for lung cancer, all three main conditions for overdiagnosis in cancer screening are present: 1) a reservoir of slowly or nongrowing lung cancer exists; 2) LDCT is a high-resolution imaging technology with the potential to identify this reservoir; and 3) eligible screening participants have a high risk of dying from causes other than lung cancer. The degree of overdiagnosis in cancer screening is most validly estimated in high-quality randomised controlled trials (RCTs), with enough follow-up time after the end of screening to avoid lead-time bias and without contamination of the control group. Nine RCTs investigating LDCT screening were identified. Two RCTs were excluded because lung cancer incidence after the end of screening was not published. Two other RCTs using active comparators were also excluded. Therefore, five RCTs were included: two trials were at low risk of bias, two of some concern and one at high risk of bias. In a meta-analysis of the two low risk of bias RCTs including 8156 healthy current or former smokers, 49% of the screen-detected cancers were overdiagnosed. There is uncertainty about this substantial degree of overdiagnosis due to unexplained heterogeneity and low precision of the summed estimate across the two trials. Key points Nine randomised controlled trials (RCTs) on low-dose computed tomography screening were identified; five were included for meta-analysis but only two of those were at low risk of bias. In a meta-analysis of recent low risk of bias RCTs including 8156 healthy current or former smokers from developed countries, we found that 49% of the screen-detected cancers may be overdiagnosed. There is uncertainty about the degree of overdiagnosis in lung cancer screening due to unexplained heterogeneity and low precision of the point estimate. If only high-quality RCTs are included in the meta-analysis, the degree of overdiagnosis is substantial. Educational aims To appreciate that low-dose computed tomography screening for lung cancer meets all three main conditions for overdiagnosis in cancer screening: a reservoir of indolent cancers exists in the population; the screening test is able to "tap" this reservoir by detecting biologically indolent cancers as well as biologically important cancers; and the population being screened is characterised by a relatively high competing risk of death from other causes To learn about biases that might affect the estimates of overdiagnosis in randomised controlled trials in cancer screening Full Article
hy The STELVIO trial, a game changer for bronchoscopic lung volume reduction in patients with severe emphysema By breathe.ersjournals.com Published On :: 2020-03-18T06:44:39-07:00 Chronic obstructive pulmonary disease (COPD) is characterised by persistent respiratory symptoms and airflow limitation, which is caused by small airway disease (bronchiolitis) and alveolar destruction (emphysema) [1]. Patients primarily suffering from severe emphysema are often limited in exercise capacity due to the consequences of hyperinflation [2]. Full Article
hy Asthma and hypercapnic respiratory failure By breathe.ersjournals.com Published On :: 2020-03-18T06:44:39-07:00 A 40-year-old, male non-smoker was diagnosed with asthma 6 years ago. He now presents with a 1-week history of worsening breathlessness with fever, cough, and purulent expectoration. He has had >10 emergency department visits and two admissions to hospital in the last 3 months. At each admission, he received bronchodilators and systemic steroids resulting in rapid improvement within 24 h. However, in the current presentation, the patient has no relief with corticosteroids and bronchodilators. His pulse is 140 per min, respiratory rate is 40 per min, blood pressure is 90/60 mmHg and room air oxygen saturation is 80%. Arterial blood gas (ABG) analysis shows hypercapnic respiratory failure. In view this respiratory failure, the patient is intubated and mechanical ventilation initiated. A chest radiograph is shown in figure 1. The therapy initiated includes bronchodilators, a systemic steroid, antibiotics and supportive care. Full Article
hy Worldwide Increase in Diagnosis of Hypertension in Children By aapgrandrounds.aappublications.org Published On :: 2020-05-01T00:59:36-07:00 Full Article
hy Neonatal Hypoglycemia Treatment Thresholds By aapgrandrounds.aappublications.org Published On :: 2020-05-01T00:59:36-07:00 Full Article
hy Levothyroxine prescribing and laboratory test use after a minor change in reference range for thyroid-stimulating hormone [Research] By www.cmaj.ca Published On :: 2020-05-03T21:05:14-07:00 BACKGROUND: Prescribing of levothyroxine and rates of thyroid function testing may be sensitive to minor changes in the upper limit of the reference range for thyroid-stimulating hormone (TSH) that increase the proportion of abnormal results. We evaluated the population-level change in levothyroxine prescribing and TSH testing after a minor planned decrease in the upper limit of the reference range for TSH in a large urban centre with a single medical laboratory. METHODS: Using provincial administrative data, we compared predicted volumes of TSH tests with actual TSH test volumes before and after a planned change in the TSH reference range. We also determined the number of new levothyroxine prescriptions for previously untreated patients and the rate of changes to the prescribed dose for those on previously stable, long-term levothyroxine therapy before and after the change in the TSH reference range. RESULTS: Before the change in the TSH reference range, actual and predicted monthly volumes of TSH testing followed an identical course. After the change, actual test volumes exceeded predicted test volumes by 7.3% (95% confidence interval [CI] 5.3%–9.3%) or about 3000 to 5000 extra tests per month. The proportion of patients with newly "abnormal" TSH results almost tripled, from 3.3% (95% CI 3.2%–3.4%) to 9.1% (95% CI 9.0%–9.2%). The rate of new levothyroxine prescriptions increased from 3.24 (95% CI 3.15–3.33) per 1000 population in 2013 to 4.06 (95% CI 3.96–4.15) per 1000 population in 2014. Among patients with preexisting stable levothyroxine therapy, there was a significant increase in the number of dose escalations (p < 0.001) and a total increase of 500 new prescriptions per month. INTERPRETATION: Our findings suggest that clinicians may have responded to mildly elevated TSH results with new or increased levothyroxine prescriptions and more TSH testing. Knowledge translation efforts may be useful to accompany minor changes in reference ranges. Full Article
hy Plasma Thymidine Kinase Activity as a Biomarker in Patients with Luminal Metastatic Breast Cancer Treated with Palbociclib within the TREnd Trial By clincancerres.aacrjournals.org Published On :: 2020-05-01T00:05:36-07:00 Purpose: Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both in vitro and in patients with ABC. Experimental Design: Modulation of TK1 levels and activity by palbociclib were studied in seven estrogen receptor–positive breast cancer cell lines: sensitive (PDS) and with palbociclib acquired resistance (PDR). TKa was assayed in plasma obtained at baseline (T0), after one cycle (T1), and at disease progression on palbociclib (T2) in patients enrolled in the "To Reverse ENDocrine Resistance" (TREnd) trial (n = 46). Results: Among E2F-dependent genes, TK1 was significantly downregulated after short-term palbociclib. Early TKa reduction by palbociclib occurred in PDS but not in PDR cells. In patients, median TKa (mTKa) at T0 was 75 DiviTum units per liter (Du/L), with baseline TKa not proving prognostic. At T1, mTKa decreased to 35 Du/L, with a minority of patients (n = 8) showing an increase—correlating with a worse outcome than those with decreased/stable TKa (n = 33; mPFS 3.0 vs 9.0 months; P = 0.002). At T2, mTKa was 251 Du/L; patients with TKa above the median had worse outcomes on post-study treatment compared with those with lower TKa (2.9 vs 8.7 months; P = 0.05). Conclusions: TK is a dynamic marker of resistance to palbociclib which may lead to early identification of patients in whom treatment escalation may be feasible. In addition, TKa may stratify prognosis in patients with acquired resistance to palbociclib. Full Article
hy Novel Insights into the Classification of Staphylococcal {beta}-Lactamases in Relation to the Cefazolin Inoculum Effect [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-04-21T08:01:10-07:00 Cefazolin has become a prominent therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, an important concern is the cefazolin inoculum effect (CzIE), a phenomenon mediated by staphylococcal β-lactamases. Four variants of staphylococcal β-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal β-lactamases and their correlation with the CzIE. We included a large collection of 690 contemporary bloodstream MSSA isolates recovered from Latin America, a region with a high prevalence of the CzIE. We determined cefazolin MICs at standard and high inoculums by broth microdilution. Whole-genome sequencing was performed to classify the β-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for β-lactamase classification and compared it to BlaZ allotypes found in unique sequences using the genomic information. Phylogenetic analyses were performed based on the BlaZ and core-genome sequences. The overall prevalence of the CzIE was 40%. Among 641 genomes, type C was the most predominant β-lactamase (37%), followed by type A (33%). We found 29 allotypes and 43 different substitutions in BlaZ. A single allotype, designated BlaZ-2, showed a robust and statistically significant association with the CzIE. Two other allotypes (BlaZ-3 and BlaZ-5) were associated with a lack of the CzIE. Three amino acid substitutions (A9V, E112A, and G145E) showed statistically significant association with the CzIE (P = <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal β-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE. Full Article
hy Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO3) Responsiveness and {beta}-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus [Susceptibility] By aac.asm.org Published On :: 2020-04-21T08:01:10-07:00 Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ~75% and ~36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. Neither intrinsic β-lactam MICs in standard Mueller-Hinton broth (MHB) nor population analysis profiles were predictive of this phenotype. Several genotypic markers (clonal complex 8 [CC8]; agr I and spa t008) were associated with NaHCO3 responsiveness for OXA. Full Article
hy Tedizolid as Step-Down Therapy following Daptomycin versus Continuation of Daptomycin against Enterococci and Methicillin- and Vancomycin-Resistant Staphylococcus aureus in a Rat Endocarditis Model [Experimental Therapeutics] By aac.asm.org Published On :: 2020-04-21T08:01:10-07:00 Tedizolid (TZD) and daptomycin (DAP) were assessed in a rat endocarditis model against Enterococcus faecalis, Enterococcus faecium (resistant to vancomycin and ampicillin), and Staphylococcus aureus. As a monotherapy, TZD for 5 days was not effective in a comparison with no-treatment controls, while DAP for 5 days was significantly effective against these bacteria. Step-down therapy (DAP for 3 days followed by TZD for 2 days) was as effective as DAP for 5 days and was comparable to 3 days of DAP plus ceftriaxone against all bacteria and to 3 days of DAP plus gentamicin against E. faecalis OG1RF. Full Article
hy A Novel Inhaled Dry-Powder Formulation of Ribavirin Allows for Efficient Lung Delivery in Healthy Participants and Those with Chronic Obstructive Pulmonary Disease in a Phase 1 Study [Antiviral Agents] By aac.asm.org Published On :: 2020-04-21T08:01:10-07:00 Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition, causing progressive decline in lung function leading to premature death. Acute exacerbations in COPD patients are predominantly associated with respiratory viruses. Ribavirin is a generic broad-spectrum antiviral agent that could be used for treatment of viral respiratory infections in COPD. Using the Particle Replication In Nonwetting Templates (PRINT) technology, which produces dry-powder particles of uniform shape and size, two new inhaled formulations of ribavirin (ribavirin-PRINT-CFI and ribavirin-PRINT-IP) were developed for efficient delivery to the lung and to minimize bystander exposure. Ribavirin-PRINT-CFI was well tolerated in healthy participants after single dosing and ribavirin-PRINT-IP was well tolerated in healthy and COPD participants after single and repeat dosing. Ribavirin-PRINT-CFI was replaced with ribavirin-PRINT-IP since the latter formulation was found to have improved physicochemical properties and it had a higher ratio of active drug to excipient per unit dose. Ribavirin concentrations were measured in lung epithelial lining fluid in both healthy and COPD participants and achieved target concentrations. Both formulations were rapidly absorbed with approximately dose proportional pharmacokinetics in plasma. Exposure to bystanders was negligible based on both the plasma and airborne ribavirin concentrations with the ribavirin-PRINT-IP formulation. Thus, ribavirin-PRINT-IP allowed for an efficient and convenient delivery of ribavirin to the lungs while minimizing systemic exposure. Further clinical investigations would be required to demonstrate ribavirin-PRINT-IP antiviral characteristics and impact on COPD viral-induced exacerbations. (The clinical trials discussed in this study have been registered at ClinicalTrials.gov under identifiers NCT03243760 and NCT03235726.) Full Article
hy Safety and Pharmacokinetic Characterization of Nacubactam, a Novel {beta}-Lactamase Inhibitor, Alone and in Combination with Meropenem, in Healthy Volunteers [Clinical Therapeutics] By aac.asm.org Published On :: 2020-04-21T08:01:10-07:00 Nacubactam is a novel β-lactamase inhibitor with dual mechanisms of action as an inhibitor of serine β-lactamases (classes A and C and some class D) and an inhibitor of penicillin binding protein 2 in Enterobacteriaceae. The safety, tolerability, and pharmacokinetics of intravenous nacubactam were evaluated in single- and multiple-ascending-dose, placebo-controlled studies. Healthy participants received single ascending doses of nacubactam of 50 to 8,000 mg, multiple ascending doses of nacubactam of 1,000 to 4,000 mg every 8 h (q8h) for up to 7 days, or nacubactam of 2,000 mg plus meropenem of 2,000 mg q8h for 6 days after a 3-day lead-in period. Nacubactam was generally well tolerated, with the most frequently reported adverse events (AEs) being mild to moderate complications associated with intravenous access and headache. There was no apparent relationship between drug dose and the pattern, incidence, or severity of AEs. No clinically relevant dose-related trends were observed in laboratory safety test results. No serious AEs, dose-limiting AEs, or deaths were reported. After single or multiple doses, nacubactam pharmacokinetics appeared linear, and exposure increased in an approximately dose-proportional manner across the dose range investigated. Nacubactam was excreted largely unchanged into urine. Coadministration of nacubactam with meropenem did not significantly alter the pharmacokinetics of either drug. These findings support the continued clinical development of nacubactam and demonstrate the suitability of meropenem as a potential β-lactam partner for nacubactam. (The studies described in this paper have been registered at ClinicalTrials.gov under NCT02134834 [single ascending dose study] and NCT02972255 [multiple ascending dose study].) Full Article
hy Hydrogen Peroxide-Mediated Oxygen Enrichment Eradicates Helicobacter pylori In Vitro and In Vivo [Experimental Therapeutics] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 Helicobacter pylori is an important risk factor for gastric ulcers. However, antibacterial therapies increase the resistance rate and decrease the eradication rate of H. pylori. Inspired by the microaerophilic characteristics of H. pylori, we aimed at effectively establishing an oxygen-enriched environment to eradicate and prevent the recurrence of H. pylori. The effect and the mechanism of an oxygen-enriched environment in eradicating H. pylori and preventing the recurrence were explored in vitro and in vivo. During oral administration and after drug withdrawal, H. pylori counts were evaluated by Giemsa staining in animal cohorts. An oxygen-enriched environment in which H. pylori could not survive was successfully established by adding hydrogen peroxide into several solutions and rabbit gastric juice. Hydrogen peroxide effectively killed H. pylori in Columbia blood agar and special peptone broth. Minimum inhibition concentrations and minimum bactericidal concentrations of hydrogen peroxide were both relatively stable after promotion of resistance for 30 generations, indicating that hydrogen peroxide did not easily promote resistance in H. pylori. In models of Mongolian gerbils and Kunming mice, hydrogen peroxide has been shown to significantly eradicate and effectively prevent the recurrence of H. pylori without toxicity and damage to the gastric mucosa. The mechanism of hydrogen peroxide causing H. pylori death was related to the disruption of bacterial cell membranes. The oxygen-enriched environment achieved by hydrogen peroxide eradicates and prevents the recurrence of H. pylori by damaging bacterial cell membranes. Hydrogen peroxide thus provides an attractive candidate for anti-H. pylori treatment. Full Article
hy Hypermutator Pseudomonas aeruginosa Exploits Multiple Genetic Pathways To Develop Multidrug Resistance during Long-Term Infections in the Airways of Cystic Fibrosis Patients [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 Pseudomonas aeruginosa exploits intrinsic and acquired resistance mechanisms to resist almost every antibiotic used in chemotherapy. Antimicrobial resistance in P. aeruginosa isolates recovered from cystic fibrosis (CF) patients is further enhanced by the occurrence of hypermutator strains, a hallmark of chronic infections in CF patients. However, the within-patient genetic diversity of P. aeruginosa populations related to antibiotic resistance remains unexplored. Here, we show the evolution of the mutational resistome profile of a P. aeruginosa hypermutator lineage by performing longitudinal and transversal analyses of isolates collected from a CF patient throughout 20 years of chronic infection. Our results show the accumulation of thousands of mutations, with an overall evolutionary history characterized by purifying selection. However, mutations in antibiotic resistance genes appear to have been positively selected, driven by antibiotic treatment. Antibiotic resistance increased as infection progressed toward the establishment of a population constituted by genotypically diversified coexisting sublineages, all of which converged to multidrug resistance. These sublineages emerged by parallel evolution through distinct evolutionary pathways, which affected genes of the same functional categories. Interestingly, ampC and ftsI, encoding the β-lactamase and penicillin-binding protein 3, respectively, were found to be among the most frequently mutated genes. In fact, both genes were targeted by multiple independent mutational events, which led to a wide diversity of coexisting alleles underlying β-lactam resistance. Our findings indicate that hypermutators, apart from boosting antibiotic resistance evolution by simultaneously targeting several genes, favor the emergence of adaptive innovative alleles by clustering beneficial/compensatory mutations in the same gene, hence expanding P. aeruginosa strategies for persistence. Full Article
hy Antimicrobial Activity of the Quinoline Derivative HT61 against Staphylococcus aureus Biofilms [Susceptibility] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 Staphylococcus aureus biofilms are a significant problem in health care settings, partly due to the presence of a nondividing, antibiotic-tolerant subpopulation. Here we evaluated treatment of S. aureus UAMS-1 biofilms with HT61, a quinoline derivative shown to be effective against nondividing Staphylococcus spp. HT61 was effective at reducing biofilm viability and was associated with increased expression of cell wall stress and division proteins, confirming its potential as a treatment for S. aureus biofilm infections. Full Article
hy Effects of Tenofovir on the Single-Dose Pharmacokinetics of Intravenous Morinidazole in Healthy Chinese Subjects [Pharmacology] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 The effects of multiple-dose administration of tenofovir disoproxil fumarate (TDF) on the pharmacokinetics of morinidazole (MOR) were compared in healthy subjects. MOR exposure was similar, with an area under the curve from 0 h to infinity (AUC0-) treatment ratio for MOR+TDF/MOR of 1.01 (90% confidence interval, 0.97 to 1.06). No relevant differences were observed regarding plasma exposure of metabolites. Renal clearances of MOR and its metabolites were not affected by TDF. No unexpected safety or tolerability issues were observed. Full Article
hy Molecular and Clinical Characterization of Multidrug-Resistant and Hypervirulent Klebsiella pneumoniae Strains from Liver Abscess in Taiwan [Epidemiology and Surveillance] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 Hypervirulent Klebsiella pneumoniae strains are the major cause of liver abscesses throughout East Asia, and these strains are usually antibiotic susceptible. Recently, multidrug-resistant and hypervirulent (MDR-HV) K. pneumoniae strains have emerged due to hypervirulent strains acquiring antimicrobial resistance determinants or the transfer of a virulence plasmid into a classic MDR strain. In this study, we characterized the clinical and microbiological properties of K. pneumoniae liver abscess (KPLA) caused by MDR-HV strains in Taiwan. Patients with community onset KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 to May 2018. Antimicrobial resistance mechanisms, capsular types, and sequence types were determined. MDR-HV strains and their parental antimicrobial-susceptible strains further underwent whole-genome sequencing (WGS) and in vivo mice lethality tests. Thirteen MDR-HV strains were identified from a total of 218 KPLA episodes. MDR-HV strains resulted in similar outcomes to antimicrobial-susceptible strains. All MDR-HV strains were traditional hypervirulent clones carrying virulence capsular types. The major resistance mechanisms were the overexpression of efflux pumps and/or the acquisition of ESBL or AmpC β-lactamase genes. WGS revealed that two hypervirulent strains had evolved to an MDR phenotype due to mutation in the ramR gene and the acquisition of an SHV-12-bearing plasmid, respectively. Both these MDR-HV strains retained high virulence compared to their parental strains. The spread of MDR-HV K. pneumoniae strains in the community raises significant public concerns, and measures should be taken to prevent the further acquisition of carbapenemase and other resistance genes among these strains in order to avoid the occurrence of untreatable KPLA. Full Article
hy The Novel Macrolide Resistance Genes mef(D), msr(F), and msr(H) Are Present on Resistance Islands in Macrococcus canis, Macrococcus caseolyticus, and Staphylococcus aureus [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 Chromosomal resistance islands containing the methicillin resistance gene mecD (McRImecD) have been reported in Macrococcus caseolyticus. Here, we identified novel macrolide resistance genes in Macrococcus canis on similar elements, called McRImsr. These elements were also integrated into the 3' end of the 30S ribosomal protein S9 gene (rpsI), delimited by characteristic attachment (att) sites, and carried a related site-specific integrase gene (int) at the 5' end. They carried novel macrolide resistance genes belonging to the msr family of ABC subfamily F (ABC-F)-type ribosomal protection protein [msr(F) and msr(H)] and the macrolide efflux mef family [mef(D)]. Highly related mef(D)-msr(F) fragments were found on diverse McRImsr elements in M. canis, M. caseolyticus, and Staphylococcus aureus. Another McRImsr-like element identified in an M. canis strain lacked the classical att site at the 3' end and carried the msr(H) gene but no neighboring mef gene. The expression of the novel resistance genes in S. aureus resulted in a low-to-moderate increase in the MIC of erythromycin but not streptogramin B. In the mef(D)-msr(F) operon, the msr(F) gene was shown to be the crucial determinant for macrolide resistance. The detection of circular forms of McRImsr and the mef(D)-msr(F) fragment suggested mobility of both the island and the resistance gene subunit. The discovery of McRImsr in different Macrococcus species and S. aureus indicates that these islands have a potential for dissemination of antibiotic resistance within the Staphylococcaceae family. Full Article
hy “What’s the Point?”: Understanding Why People With Type 2 Diabetes Decline Structured Education By clinical.diabetesjournals.org Published On :: 2020-04-15T12:00:21-07:00 Structured diabetes education (SDE) is an evidence-based intervention that supports self-management in people with type 2 diabetes. In the United Kingdom, health care providers working in primary care settings are responsible for referring people with type 2 diabetes to SDE programs. However, national audits record a high percentage of nonattenders. We explored the personal experience of living with type 2 diabetes that led to individuals declining invitations to attend SDE programs. The themes suggested that emotional, cognitive, and social issues related to diagnosis and living with diabetes may be responsible for declining to attend SDE and that these factors may be masked by explanations of practical barriers. A person-centered approach to understanding the personal meaning of being diagnosed and living with type 2 diabetes may help to identify individuals’ psychosocial barriers to attending SDE. Full Article
hy Objectively-Measured Light-Intensity Physical Activity and Risk of Cancer Mortality: A Meta-analysis of Prospective Cohort Studies By cebp.aacrjournals.org Published On :: 2020-05-01T00:05:36-07:00 Background: The impact of light-intensity physical activity (LPA) in preventing cancer mortality has been questioned. To address this concern, the present meta-analysis aimed to quantify the association between objectively-measured LPA and risk of cancer mortality. Methods: We conducted a systematic literature search in PubMed and Scopus to January 2020. Prospective cohort studies reporting the association between objectively-measured LPA using activity monitors (e.g., accelerometers) and risk of cancer mortality in the general population were included. The summary hazard ratios (HR) per 30 min/day of LPA and 95% confidence intervals (CI) were obtained using a random-effects model. Dose–response analysis was used to plot their relationship. Results: Five prospective cohort studies were included, in which the definition of LPA based on accelerometer readings was mainly set within 100 to 2,100 counts/min. The summary HR for cancer mortality per 30 min/day of LPA was 0.86 (95% CI, 0.79–0.95; I2 < 1%), and the association between LPA and risk reduction in cancer mortality was linearly shaped (Pnonlinearity = 0.72). LPA exhibited a comparable magnitude of risk reduction in cancer mortality of moderate-to-vigorous physical activity regardless of equal time-length (0.87 per 30 min/day vs. 0.94 per 30 min/day, Pinteraction = 0.46) or equal amount (0.74 vs. 0.94 per 150 metabolic equivalents-min/day, Pinteraction = 0.11). Furthermore, replacing sedentary time by LPA of 30 min/day decreased the risk of cancer mortality by 9%. Conclusions: Objectively-measured LPA conferred benefits in decreasing the risk of cancer mortality. Impact: LPA should be considered in physical activity guidelines to decrease the risk of cancer mortality. Full Article
hy Purification of Recombinant Adeno-Associated Virus 2 (rAAV2) by Heparin Column Affinity Chromatography By cshprotocols.cshlp.org Published On :: 2020-05-01T06:29:31-07:00 This protocol describes a simple single-step column purification (SSCP) of rAAV2 by gravity flow based on its affinity to heparin, without ultracentrifugation. Full Article
hy Radiomics Study of Thyroid Ultrasound for Predicting BRAF Mutation in Papillary Thyroid Carcinoma: Preliminary Results [FUNCTIONAL] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: It is not known how radiomics using ultrasound images contribute to the detection of BRAF mutation. This study aimed to evaluate whether a radiomics study of gray-scale ultrasound can predict the presence or absence of B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation in papillary thyroid cancer. MATERIALS AND METHODS: The study retrospectively included 96 thyroid nodules that were surgically confirmed papillary thyroid cancers between January 2012 and June 2013. BRAF mutation was positive in 48 nodules and negative in 48 nodules. For analysis, ROIs from the nodules were demarcated manually on both longitudinal and transverse sonographic images. We extracted a total of 86 radiomics features derived from histogram parameters, gray-level co-occurrence matrix, intensity size zone matrix, and shape features. These features were used to build 3 different classifier models, including logistic regression, support vector machine, and random forest using 5-fold cross-validation. The performance including accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve, of the different models was evaluated. RESULTS: The incidence of high-suspicion nodules diagnosed on ultrasound was higher in the BRAF mutation–positive group than in the mutation–negative group (P = .004). The radiomics approach demonstrated that all classification models showed moderate performance for predicting the presence of BRAF mutation in papillary thyroid cancers with an area under the curve value of 0.651, accuracy of 64.3%, sensitivity of 66.8%, and specificity of 61.8%, on average, for the 3 models. CONCLUSIONS: Radiomics study using thyroid sonography is limited in predicting the BRAF mutation status of papillary thyroid carcinoma. Further studies will be needed to validate our results using various diagnostic methods. Full Article
hy Assessment of Apparent Internal Carotid Tandem Occlusion on High-Resolution Vessel Wall Imaging: Comparison with Digital Subtraction Angiography [EXTRACRANIAL VASCULAR] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: Not all tandem occlusions diagnosed on traditional vascular imaging modalities, such as MRA, represent actual complete ICA occlusion. This study aimed to explore the utility of high-resolution vessel wall imaging in identifying true ICA tandem occlusions and screening patients for their suitability for endovascular recanalization. MATERIALS AND METHODS: Patients with no signal in the ICA on MRA were retrospectively reviewed. Two neuroradiologists independently reviewed their high-resolution vessel wall images to assess whether there were true tandem occlusions and categorized all cases into intracranial ICA occlusion, extracranial ICA occlusion, tandem occlusion, or near-occlusion. DSA classified patient images into the same 4 categories, which were used as the comparison with high-resolution vessel wall imaging. The suitability for recanalization of occluded vessels was evaluated on high-resolution vessel wall imaging compared with DSA. RESULTS: Forty-five patients with no ICA signal on MRA who had available high-resolution vessel wall imaging and DSA images were included. Among the 34 patients (34/45, 75.6%) with tandem occlusions on DSA, 18 cases also showed tandem occlusions on high-resolution vessel wall imaging. The remaining 16 patients, intracranial ICA, extracranial ICA occlusions and near-occlusions were found in 2, 6, and 8 patients, respectively, on the basis of high-resolution vessel wall imaging. A total of 20 cases (20/45, 44.4%) were considered suitable for recanalization on the basis of both DSA and high-resolution vessel wall imaging. Among the 25 patients deemed unsuitable for recanalization by DSA, 11 were deemed suitable for recanalization by high-resolution vessel wall imaging. CONCLUSIONS: High-resolution vessel wall imaging could allow identification of true ICA tandem occlusion in patients with an absence of signal on MRA. Findings on high-resolution vessel wall imaging can be used to screen more suitable candidates for recanalization therapy. Full Article
hy Intermixed Dimethyl-Sulfoxide-Based Nonadhesive Liquid Embolic Agents Delivered Serially via the Same Microcatheter for Cerebral AVM Treatment [INTERVENTIONAL] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: Conventional nonadhesive liquid embolic agents currently are the criterion standard for endovascular embolization of cerebral AVMs. However, inadequate distal penetration into the nidus and unstable proximal plug formation are the major limitations of this approach and of the currently available embolic materials. The aim of this study was to evaluate the hypothetic efficacy of combining liquid embolic agents with different properties and viscosities for use in endovascular embolization of cerebral AVMs. MATERIALS AND METHODS: From March 2018 to March 2019, sixteen patients with cerebral AVMs (12 women, 4 men; age range, 33–61 years) underwent endovascular embolization with combined liquid embolic agents delivered serially via a single microcatheter. The procedure consists of initial embolization with PHIL 30%, followed by Menox 18 through the same microcatheter. According to the Spetzler-Martin scale, 11 (68.75%) AVMs were grades I–II, 4 (25%) were grade III, and 1 (6.25%) was grade IV. Angiographic, technical, and clinical outcomes were analyzed independently. RESULTS: Combined PHIL and Menox embolization through the same microcatheter via 21 pedicles was performed in these 16 patients. Once the length of the reflux reached approximately 2 cm, PHIL 30% was switched to Menox 18. Antegrade flow and distal penetration of the serially applied liquid embolic agents were observed in all 16 cases. The ability to completely control the flow of the materials and avoid any dangerous proximal reflux was noted in all performed embolizations. The estimated average size reduction of the treated AVMs was 85%, ranging from 50% to 100%. Complete embolization was achieved in 10/16 or 62.5% of the cases. There was no procedure-related complication during or after the embolization. No mortality or postprocedural clinical worsening was seen. Clinical success and complete obliteration were confirmed with at least 1 follow-up angiography in 10/16 patients. CONCLUSIONS: Serial delivery of nonadhesive liquid embolic agents via the same microcatheter was safe and effective in our study and may be a potential technique for routine AVM treatment. However, further investigations are required to validate the safety and the efficacy of the method. Full Article
hy Save the Brain First: CTA and Mechanical Thrombectomy in Patients at Risk for Contrast-Induced Nephropathy [article-commentary] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 Full Article
hy Reliability of CT Angiography in Cerebral Vasospasm: A Systematic Review of the Literature and an Inter- and Intraobserver Study [INTERVENTIONAL] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm. MATERIALS AND METHODS: In Part I, articles reporting the reliability of CTA up to May 2018 were systematically searched and evaluated. In Part II, 11 raters independently graded 17 arterial segments in each of 50 patients with SAH for the presence of vasospasm using a 4-category scale. Raters were additionally asked to judge the presence of any moderate/severe vasospasm (≥ 50% narrowing) and whether findings would justify augmentation of medical treatment or conventional angiography ± balloon angioplasty. Four raters took part in the intraobserver reliability study. RESULTS: In Part I, the systematic review revealed few studies with heterogeneous vasospasm definitions. In Part II, we found interrater reliability to be moderate at best ( ≤ 0.6), even when results were stratified according to specialty and experience. Intrarater reliability was substantial ( > 0.6) in 3/4 readers. In the per arterial segment analysis, substantial agreement was reached only for the middle cerebral arteries, and only when senior raters’ judgments were dichotomized (presence or absence of ≥50% narrowing). Agreement on the medical or angiographic management of vasospasm based on CTA alone was less than substantial ( ≤ 0.6). CONCLUSIONS: The diagnosis of vasospasm using CTA alone was not sufficiently repeatable among observers to support its general use to guide decisions in the clinical management of patients with SAH. Full Article
hy CT Angiography in Evaluating Large-Vessel Occlusion in Acute Anterior Circulation Ischemic Stroke: Factors Associated with Diagnostic Error in Clinical Practice [INTERVENTIONAL] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 BACKGROUND AND PURPOSE: It is currently not completely clear how well radiologists perform in evaluating large-vessel occlusion on CTA in acute ischemic stroke. The purpose of this study was to investigate potential factors associated with diagnostic error. MATERIALS AND METHODS: Five hundred twenty consecutive patients with a clinical diagnosis of acute ischemic stroke (49.4% men; mean age, 72 years) who underwent CTA to evaluate large-vessel occlusion of the proximal anterior circulation were included. CTA scans were retrospectively reviewed by a consensus panel of 2 neuroradiologists. Logistic regression analysis was performed to investigate the association between several variables and missed large-vessel occlusion at the initial CTA interpretation. RESULTS: The prevalence of large-vessel occlusion was 16% (84/520 patients); 20% (17/84) of large-vessel occlusions were missed at the initial CTA evaluation. In multivariate analysis, non-neuroradiologists were more likely to miss large-vessel occlusion compared with neuroradiologists (OR = 5.62; 95% CI, 1.06–29.85; P = .04), and occlusions of the M2 segment were more likely to be missed compared with occlusions of the distal internal carotid artery and/or M1 segment (OR = 5.69; 95% CI, 1.44–22.57; P = .01). There were no calcified emboli in initially correctly identified large-vessel occlusions. However, calcified emboli were present in 4 of 17 (24%) initially missed or misinterpreted large-vessel occlusions. CONCLUSIONS: Several factors may have an association with missing a large-vessel occlusion on CTA, including the CTA interpreter (non-neuroradiologists versus neuroradiologists), large-vessel occlusion location (M2 segment versus the distal internal carotid artery and/or M1 segment), and large-vessel occlusion caused by calcified emboli. Awareness of these factors may improve the accuracy in interpreting CTA and eventually improve stroke outcome. Full Article
hy MR Thermometry in Cerebrovascular Disease: Physiologic Basis, Hemodynamic Dependence, and a New Frontier in Stroke Imaging [ADULT BRAIN] By www.ajnr.org Published On :: 2020-04-09T06:30:48-07:00 SUMMARY: The remarkable temperature sensitivity of the brain is widely recognized and has been studied for its role in the potentiation of ischemic and other neurologic injuries. Pyrexia frequently complicates large-vessel acute ischemic stroke and develops commonly in critically ill neurologic patients; the profound sensitivity of the brain even to minor intraischemic temperature changes, together with the discovery of brain-to-systemic as well as intracerebral temperature gradients, has thus compelled the exploration of cerebral thermoregulation and uncovered its immutable dependence on cerebral blood flow. A lack of pragmatic and noninvasive tools for spatially and temporally resolved brain thermometry has historically restricted empiric study of cerebral temperature homeostasis; however, MR thermometry (MRT) leveraging temperature-sensitive nuclear magnetic resonance phenomena is well-suited to bridging this long-standing gap. This review aims to introduce the reader to the following: 1) fundamental aspects of cerebral thermoregulation, 2) the physical basis of noninvasive MRT, and 3) the physiologic interdependence of cerebral temperature, perfusion, metabolism, and viability. Full Article
hy Why is HCMC real estate more attractive than Hanoi? By batdongsan.com.vn Published On :: 16:47 15/10/2019 On October 15, Batdongsan.com.vn released Hanoi Real Estate Market Report for Q3/2019, reporting that the asking price and growth rate of Hanoi market are lower than that of Ho Chi Minh City. Full Article
hy Digital storytelling: Selling properties with ease in a hyper-connected world By batdongsan.com.vn Published On :: 17:34 04/03/2020 Three marketing experts share their unconventional means of capturing the attention of potential homeowners of today. Full Article
hy Green buildings are crucial to addressing climate change, but why aren’t we seeing more of them? By batdongsan.com.vn Published On :: 09:56 05/05/2020 We spoke with industry experts to identify what’s preventing developers from fully going green – and it all boils down to lack of finances. Full Article
hy Why you should hire a real estate agent? By batdongsan.com.vn Published On :: 16:48 11/09/2019 Buying a home always need time and effort. Many home buyers can not manage a series of buying steps themselves, so hiring real estate agents to finish the deal quickly and more effectively is a smart decision. If you are still considering whether you should hire an agent or not, the following infographic will show you the benefits of buying a home with an agent: Full Article
hy Park Hyatt Phú Quốc By batdongsan.com.vn Published On :: Tue, 19 Nov 2019 15:35:30 GMT Khu nghỉ dưỡng Park Hyatt Phú Quốc là dự án của chủ đầu tư BIM Group được phát triển với quy mô gồm 110 phòng khách sạn và 65 căn biệt thự nghỉ dưỡng hạng sang tại đảo ngọc Phú Quốc, dự kiến đi vào hoạt động trong năm 2022. Full Article
hy Why Interior Design Is Essential When Listing Your Home By batdongsan.com.vn Published On :: 11:35 03/03/2015 The decision to list your home for resale is a big one. No doubt it came about after much thought, weighing pros and cons, and series of long discussions. However, once you decide to put your home on the market, get ready for the next big discussion: interior design. Full Article
hy Real estate agents reveal 11 reasons why your home is unsellable By batdongsan.com.vn Published On :: 17:22 20/08/2019 Business Insider asked real-estate agents across the U.S., and they point out 11 reason that prevent your home from being sold. Full Article
hy The eLearning Guild is now The Learning Guild. Here’s Why. By feedproxy.google.com Published On :: Sat, 09 May 2020 11:06:03 +0000 On May 7th, we announced a change to our brand from the eLearning Guild to the Learning Guild. As a member of our community, you […] The post The eLearning Guild is now The Learning Guild. Here’s Why. appeared first on e-Learning Feeds. Full Article eLearning Trends brand eLearning Guild Guild Inside the Guild learning
hy SpeakerChat for 05/15/20: Spaced Learning – Why It’s So Good & How to Get Started By feedproxy.google.com Published On :: Sat, 09 May 2020 11:10:03 +0000 We're bringing you something new: SpeakerChat. This event is both a way to revisit some great eLearning Guild content from a recorded session while also […] The post SpeakerChat for 05/15/20: Spaced Learning – Why It’s So Good & How to Get Started appeared first on e-Learning Feeds. Full Article eLearning Trends email campaigns Instructional Design Mike Taylor Research Spaced Learning SpeakerChat
hy What is Employee Development, and Why is it Important? By feedproxy.google.com Published On :: Sat, 09 May 2020 15:16:03 +0000 Unlike for previous generations, career development doesn’t only happen in educational institutions. The more we work, the more we realize our passion and discover the […] The post What is Employee Development, and Why is it Important? appeared first on e-Learning Feeds. Full Article eLearning Companies Employee Development And Retention
hy Hyundai की अनोखी पेशकश, लॉकडाउन के दौरान गई नौकरी, तो तीन माह तक नहीं देनी होगी नई कार की EMI! By www.amarujala.com Published On :: Wed, 06 May 2020 05:30:04 +0530 Hyundai Motor India (ह्यूंदै मोटर इंडिया) ने अनिश्चितता के मौजूदा समय में ग्राहकों का विश्वास बढ़ाने के लिए एक अनोखे Hyundai EMI Assurance (ह्यूंदै ईएमआई आश्वासन) कार्यक्रम का एलान किया है, जो ऑटोमोबाइल उद्योग में पहली बार पेश किया गया है। Full Article
hy Hyundai दे रही है अपनी कारों पर 1 लाख रुपये तक का बंपर डिस्काउंट, खरीदें मनपसंद कार By www.amarujala.com Published On :: Thu, 07 May 2020 05:27:08 +0530 Hyundai अपने कई मॉडल्स पर मई के महीने में एक लाख रुपये तक के डिस्काउंट और ऑफर्स दे रही है। यहां जानते हैं कि Hyundai के कौन से मॉडल्स पर कितना डिस्काउंट मिल रहा है। Full Article
hy Hyundai motor ने अपने ग्राहकों के लिए शुरू की ये 5 स्कीम, कार खरीदने का है बेहतर मौका By www.amarujala.com Published On :: Sat, 09 May 2020 02:16:24 +0530 आपके पास Hyundai की कार खरीदने का एक बेहतरीन मौका है। दरअसल कंपनी ने अपने ग्राहकों के लिए 5 अनूठी कार फाइनेंस स्कीम का एलान किया है। Full Article
hy लंबे समय बाद Hyundai ने शुरू किया प्लांट, पहले दिन ही बनाईं 200 कारें By www.amarujala.com Published On :: Sat, 09 May 2020 04:40:09 +0530 लंबे समय बाद एक बार फिर ऑटो कंपनियों ने अपने कारखाने खोलने शुरू कर दिये हैं। ह्यूंदै मोटर इंडिया ने कहा कि उसके चेन्नई कारखाने का परिचालन फिर से शुरू हो गया है। Full Article
hy Sophie Marschner turns real-world data into a digital topography in Monolith By www.factmag.com Published On :: Thu, 07 May 2020 11:00:00 +0000 Generative visuals and eerie sound design based on height maps of glaciers, canyons and estuaries. London-based motion graphic designer Sophie Marschner transforms real-world data into a delicate digital topography in Monolith. By using the height maps of various large-scale landmarks, including glaciers, canyons and estuaries, Marschner maps the outside world into a more intimate, digital […] The post Sophie Marschner turns real-world data into a digital topography in Monolith appeared first on FACT Magazine. Full Article Series Audiovisual Featured Stories Featured Top sticky1 Sophie Marschner Scotch Mist
hy GPS face-off: Why countries are vying to rule the skies with satnav By www.newscientist.com Published On :: Wed, 12 Feb 2020 10:00:00 +0000 A geopolitical battle is being played out in orbit as countries vie for the best satellite navigation system Full Article
hy Why people become strangely attached to their robot vacuum cleaners By www.newscientist.com Published On :: Wed, 18 Mar 2020 18:00:00 +0000 Kate Darling researches human-robot interaction. She explains why we are prone to forming emotional connections with robots and what we can learn from our relationships with pets and other animals Full Article