Palliative Care in the Pediatric Intensive Care Unit.

The purposes of this review are to describe differences between palliative care for adult patients and palliative care for pediatric patients, both generally and in the intensive care unit; to highlight ethical considerations for pediatric intensive care unit patients by using illustrative cases; and to examine the impact of these ethical considerations on decision-making for children and their families.

Clinicopathologic Correlation of CD44 + /CD24 - Expression in Breast Cancer: a Report from Tertiary Care Medical University in India.

CD44 + /CD24 - phenotype has been associated with stem cell-like characteristics with enhanced invasive properties, radiation resistance, and with distinct genetic profiles suggesting a correlation to adverse prognosis in western literature. The aim of this study was to study CD44 + /CD24 - phenotype as an adverse prognostic marker in Indian breast cancer patients. N = 61 breast cancer patients included in a tertiary care facility in India were evaluated for receptor studies (estrogen receptor ER, progesterone receptor PR, Herceptin antibody Her2 neu receptor, CD44 & CD24 stem cell markers). CD44 + /CD24 - phenotype was statistically related to adverse factors like estrogen and progesterone receptors non-expression, her 2 neu expression, and triple-negative breast cancer. Of the 39 patients with ER-ve status, 33 (84.6%) were found to have CD44 + /CD24 - phenotype and 82.5% of all the CD 44 + /CD24 - patients were ER negative (p = 0.001). Thirty-four (75.5%) of the PR-ve patients showed the CD44 + /CD24 - phenotype, and of all the CD 44 + /CD24 - patients, 85% of were PR negative (p = 0.006). Thirty-six (75%) of Her-2-Neu + ve were CD44 + /CD24 - . Approximately 90% of the Her 2 Neu patients expressed CD44 + /CD24 - and 76.9% of all the triple-negative patients were found to be CD44 + /CD24 - expression (p = 0.001). CD44 + /CD24 - had a significant association with adverse prognostic factors like stage of disease, hormonal receptor status, and molecular subtypes in Indian breast cancer patients like the Western data.

MALDI-TOF Mass Spectrometric Detection of SARS-CoV-2 Using Cellulose Sulfate Ester Enrichment and Hot Acid Treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here we report a novel strategy for the rapid detection of SARS-CoV-2 based on an enrichment approach exploiting the affinity between the virus and cellulose sulfate ester functional groups, hot acid hydrolysis, and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Virus samples were enriched using cellulose sulfate ester microcolumns. Virus peptides were prepared using the hot acid aspartate-selective hydrolysis and characterized by MALDI-TOF MS. Collected spectra were processed with a peptide fingerprint algorithm, and searching parameters were optimized for the detection of SARS-CoV-2. These peptides provide high sequence coverage for nucleocapsid (N protein) and allow confident identification of SARS-CoV-2. Peptide markers contributing to the detection were rigorously identified using bottom-up proteomics. The approach demonstrated in this study holds the potential for developing a rapid assay for COVID-19 diagnosis and detecting virus variants from a variety of sources, such as sewage and nasal swabs.

Visible blue light inhibits infection and replication of SARS-CoV-2 at doses that are well-tolerated by human respiratory tissue.

The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that primary 3D human tracheal/bronchial-derived epithelial tissues tolerated high doses of a narrow spectral band of visible light centered at a peak wavelength of 425 nm. We extended these studies to Vero E6 cells to understand how light may influence the viability of a mammalian cell line conventionally used for assaying SARS-CoV-2. The exposure of single-cell monolayers of Vero E6 cells to similar doses of 425 nm blue light resulted in viabilities that were dependent on dose and cell density. Doses of 425 nm blue light that are well-tolerated by Vero E6 cells also inhibited infection and replication of cell-associated SARS-CoV-2 by > 99% 24 h post-infection after a single five-minute light exposure. Moreover, the 425 nm blue light inactivated cell-free betacoronaviruses including SARS-CoV-1, MERS-CoV, and SARS-CoV-2 up to 99.99% in a dose-dependent manner. Importantly, clinically applicable doses of 425 nm blue light dramatically inhibited SARS-CoV-2 infection and replication in primary human 3D tracheal/bronchial tissue. Safe doses of visible light should be considered part of the strategic portfolio for the development of SARS-CoV-2 therapeutic countermeasures to mitigate coronavirus disease 2019 (COVID-19).

Scottish consensus statement on the role of FeNO in adult asthma.

Fractional exhaled nitric oxide (FeNO) is the only available point of care test to assess type-2 inflammation in asthma. In making a diagnosis of asthma, FeNO should be used together with blood eosinophils and spirometry, alongside a history. Raised FeNO in conjunction with blood eosinophilia are treatable traits of type 2 inflammation in asthma, which in turn may guide personalised management. A FeNO suppression test can be used to assess adherence and device use with ICS therapy. Furthermore FeNO may be used to provide feedback to patients in response to ICS, especially when spirometry is normal. FeNO may facilitate appropriate referral to secondary care for more definitive specialist investigations. In summary, FeNO is cost effective in the diagnosis and management of asthma and should be incorporated into primary and secondary care as part of routine clinical practice.

Pilot of a Pediatric Palliative Care Early Intervention Instrument.

Current research demonstrates that pediatric symptom management care is often initiated in the late stages of disease once clinicians are no longer able to meaningfully impact symptom burden. Given that physicians or nurse practitioners are responsible for initiating palliative care referrals, it is incumbent upon registered nurses to advocate when improved symptom management care is needed. The pediatric palliative care screening instrument pilot provides a centralized instrument to document and quantify a patient's symptom profile, giving registered nurses the opportunity to objectively communicate and track a patient's need for improved symptom management care within the areas of pain, secretions, dyspnea, intractable seizures, nausea, vomiting, constipation, diarrhea, anorexia, cachexia, sleep disturbance, lethargy, anxiety, depression, and/or agitation. The 4-week quality improvement project at an academic teaching hospital formally incorporated the bedside registered nurses' symptom assessment into a centralized document. Fifty-three patients were identified as having an uncontrolled symptom burden in at least one of the symptom domains, indicating that excessive and untreated symptom burden was present on the acute care floor. The pediatric palliative care screening instrument could act as a conduit between bedside registered nurses and the palliative care team, serving to reduce the time between onset of excessive symptom burden and initiation of symptom management services.

Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort.

Comorbidities, are common in COPD, have been associated with poor outcomes and are thought to relate to systemic inflammation. To investigate comorbidities in relation to systemic inflammation and outcomes we recorded comorbidities in a well characterized cohort (ECLIPSE study) for 2164 clinically stable COPD subjects, 337 smokers and 245 non-smokers with normal lung function. COPD patients had a higher prevalence of osteoporosis, anxiety/panic attacks, heart trouble, heart attack, and heart failure, than smokers or nonsmokers. Heart failure (Hazard Ratio [HR] 1.9, 95% Confidence Interval [CI] 1.3-2.9), ischemic heart disease (HR 1.5, 95% CI 1.1-2.0), heart disease (HR 1.5, 95% CI 1.2-2.0), and diabetes (HR 1.7, 95% CI 1.2-2.4) had increased odds of mortality when coexistent with COPD. Multiple comorbidities had accumulative effect on mortality. COPD and cardiovascular disease was associated with poorer quality of life, higher MRC dyspnea scores, reduced 6MWD, higher BODE index scores. Osteoporosis, hypertension and diabetes were associated with higher MRC dyspnea scores and reduced 6MWD. Higher blood concentrations of fibrinogen, IL-6 and IL-8 levels occurred in those with heart disease. Comorbidity is associated with poor clinical outcomes in COPD. The comorbidities of heart disease, hypertension and diabetes are associated with increased systemic inflammation.

Emergence and genetic variation of neuraminidase stalk deletions in avian influenza viruses.

When avian influenza viruses (AIVs) are transmitted from their reservoir hosts (wild waterfowl and shorebirds) to domestic bird species, they undergo genetic changes that have been linked to higher virulence and broader host range. Common genetic AIV modifications in viral proteins of poultry isolates are deletions in the stalk region of the neuraminidase (NA) and additions of glycosylation sites on the hemagglutinin (HA). Even though these NA deletion mutations occur in several AIV subtypes, they have not been analyzed comprehensively. In this study, 4,920 NA nucleotide sequences, 5,596 HA nucleotide and 4,702 HA amino acid sequences were analyzed to elucidate the widespread emergence of NA stalk deletions in gallinaceous hosts, the genetic polymorphism of the deletion patterns and association between the stalk deletions in NA and amino acid variants in HA. Forty-seven different NA stalk deletion patterns were identified in six NA subtypes, N1-N3 and N5-N7. An analysis that controlled for phylogenetic dependence due to shared ancestry showed that NA stalk deletions are statistically correlated with gallinaceous hosts and certain amino acid features on the HA protein. Those HA features included five glycosylation sites, one insertion and one deletion. The correlations between NA stalk deletions and HA features are HA-NA-subtype-specific. Our results demonstrate that stalk deletions in the NA proteins of AIV are relatively common. Understanding the NA stalk deletion and related HA features may be important for vaccine and drug development and could be useful in establishing effective early detection and warning systems for the poultry industry.

Airway dimensions in COPD: relationships with clinical variables.

BACKGROUND: COPD patients have varying degrees of airways disease and emphysema. CT scanning can differentiate these pathological subtypes. We evaluated airway dimensions and emphysema severity with low dose CT scanning in COPD patients to determine relationships with clinical features of the disease. METHODS: Fifty six patients with COPD had a low dose thoracic CT scan. Airways were analysed using novel software as either proximal (1st and 2nd generation) or distal (3rd to 6th generation); the extent of emphysema was assessed as the percentage of pixels less than -950 Hounsfield units. CT measures were related to clinical features of COPD. RESULTS: Thicker walls in the proximal airways were associated with clinical features that may represent a bronchitic phenotype (MRC Bronchitis Score; ß = 0.20, p = 0.003, Frequent Exacerbations; ß = 0.14, p = 0.017, Total St George's Score; ß = 0.50, p = 0.001 and body mass index [BMI]; ß = 0.26, p = 0.049); these associations were independent of emphysema. BMI was negatively correlated with the degree of emphysema (ß = -0.41, p = 0.001). Airway wall thickness was negatively correlated with CT measured emphysema for both proximal and more distal airways (r = -0.30, p = 0.025 and r = -0.32, p = 0.015). CONCLUSIONS: CT measured airway dimensions are associated with several clinical measures of COPD; these are related to a bronchitic phenotype and the effect is independent of emphysema.

Identifying errors in avian influenza virus gene sequences and implications for data usage of public databases.

Public gene sequence databases have become important research tools to understand viruses and other organisms. Evidence suggests that the identifying information for some of the sequences in these databases might not belong to the sequences they are associated with. We developed two tests to conduct a comprehensive analysis of all published sequences of the hemaglutinin and neuramidase genes of avian influenza viruses (AIVs) to identify sequences that may have been misclassified. One test identified sequence pairs with highly similar nucleotide sequences despite a difference of several years between their sampling dates. Another test, which was applied to samples sequenced and deposited more than once, detected sequences with more nucleotide differences to their own than to their closest relatives. All sequences identified as misclassified were further traced to relevant publications to assess the likelihood of contamination and determine if any conclusions were associated with the use of these sequences. Our results suggested that among 4040 published gene sequences examined, approximately 0.8% might be misclassified and that publications using these sequences may include inaccurate statements. Findings from this report suggest that using laboratory-adapted strains and handling multiple samples simultaneously increases the risk of contamination. The tests reported here may be useful for screening new submissions to public sequence databases.

Invasions by Eurasian avian influenza virus H6 genes and replacement of the virus' North American clade.

The spread of highly pathogenic avian influenza virus (AIV) (H5N1) underlines the potential for global AIV movement through birds. The phylogenies of AIV genes from avian hosts usually separate into Eurasian and North American clades, reflecting limited bird migration between the hemispheres. However, mounting evidence that some H6 sequences from North America cluster with Eurasian subtype H6 sequences calls the strict hemispheric divide into question. We conducted a comprehensive phylogenetic analysis of the extent and timing of cross-hemisphere movements by the H6 gene. Results suggested that Eurasian H6 subtype has invaded North America several times, with the first invasions occurring 10 years before the first detection of invading isolates. The members of the North American clade decreased from 100% in the 1980s to 20% in the 2000s among H6 isolates from North America. Unraveling the reasons for this large-scale gene movement between hemispheres might identify drivers of global AIV circulation.

Arterial stiffness is independently associated with emphysema severity in patients with chronic obstructive pulmonary disease.

RATIONALE: More patients with chronic obstructive pulmonary disease (COPD) die of cardiovascular causes than of respiratory causes, and patients with COPD have increased morbidity and mortality from stroke and coronary heart disease. Arterial stiffness independently predicts cardiovascular risk, is associated with atheromatous plaque burden, and is increased in patients with COPD compared with control subjects matched for cardiovascular risk factors. Elastin fragmentation and changes in collagen are found in the connective tissue of both emphysematous lungs and stiff arteries, but it is not known whether the severity of arterial stiffness in patients with COPD is associated with the severity of emphysema. OBJECTIVES: To identify whether the extent of arterial stiffness is associated with emphysema severity. METHODS: We performed a cross-sectional study in 157 patients with COPD. MEASUREMENTS AND MAIN RESULTS: We measured pulse wave velocity (a validated measure of arterial stiffness), blood pressure, smoking pack-years, glucose, cholesterol, and C-reactive protein in 157 patients with COPD. We assessed emphysema using quantitative computed tomography scanning in a subgroup of 73 patients. We found that emphysema severity was associated with arterial stiffness (r = 0.471, P < 0.001). The association was independent of smoking, age, sex, FEV(1)% predicted, highly sensitive C-reactive protein and glucose concentrations, cholesterol-high-density lipoprotein ratio, and pulse oximetry oxygen saturations. CONCLUSIONS: Emphysema severity is associated with arterial stiffness in patients with COPD. Similar pathophysiological processes may be involved in both lung and arterial tissue and further studies are now required to identify the mechanism underlying this newly described association.

A glycomics platform for the analysis of permethylated oligosaccharide alditols.

This communication reports the development of an LC/MS platform for the analysis of permethylated oligosaccharide alditols that, for the first time, demonstrates routine online oligosaccharide isomer separation of these compounds before introduction into the mass spectrometer. The method leverages a high-resolution liquid chromatography system with the superior fragmentation pattern characteristics of permethylated oligosaccharide alditols that are dissociated under low-energy collision conditions using quadrupole orthogonal time-of-flight (QoTOF) instrumentation and up to pseudo MS(3) mass spectrometry. Glycoforms, including isomers, are readily identified and their structures assigned. The isomer-specific spectra include highly informative cross-ring and elimination fragments, branch position specific signatures, and glycosidic bond fragments, thus facilitating linkage, branch, and sequence assignment. The method is sensitive and can be applied using as little as 40 fmol of derivatized oligosaccharide. Because permethylation renders oligosaccharides nearly chemically equivalent in the mass spectrometer, the method is semiquantitative and, in this regard, is comparable to methods reported using high field NMR and capillary electrophoresis. In this postgenomic age, the importance of glycosylation in biological processes has become clear. The nature of many of the important questions in glycomics is such that sample material is often extremely limited, thus necessitating the development of highly sensitive methods for rigorous structural assignment of the oligosaccharides in complex mixtures. The glycomics platform presented here fulfills these criteria and should lead to more facile glycomics analyses.

A multi-species epidemic model with spatial dynamics.

A model is formulated that describes the spatial propagation of a disease that can be transmitted between multiple species. The spatial component consists, for each species, of a certain number of patches that make up the vertices of a digraph, the arcs of which represent the movement of the various species between the patches. In each of the patches and for each species, a susceptible-exposed-infectious-recovered (SEIR) epidemic model describes the evolution of the disease status of individuals. Also in each patch, there is transmission of the disease from species to species. An analysis of the system is given, beginning with results on the mobility component. A formula is derived for the computation of the basic reproduction number R(0) for sspecies and npatches, which then determines the global stability properties of the disease free equilibrium. Simulations for the spread of a disease in one species and two patches are presented.

A survey of refugee health assessments in the United States.

We conducted a survey among nine geographically dispersed, large metropolitan refugee health programs to estimate the number of U.S. refugee arrivals during 1997 and 1998, the number receiving health assessments, and the percentage of sites offering health services. The nine sites received an estimated 40% of all U.S. refugee arrivals during the study period. Of these refugees, 76% received a health assessment. The completeness of health assessments, including services offered, varied by site; some services were provided by the private sector. Most sites offered services for infectious diseases and vaccinations. While 78% of the sites offered mental health care, but only 33% actually performed mental status examinations. These statistics show that such health services need to be provided on a broader basis and possibly reflect a need to address cultural and language barriers that might be preventing their delivery to this diverse population.

Large summertime influenza A outbreak among tourists in Alaska and the Yukon Territory.

We investigated a large summertime outbreak of acute respiratory illness during May-September 1998 in Alaska and the Yukon Territory, Canada. Surveillance for acute respiratory illness (ARI), influenza-like illness (ILI), and pneumonia conducted at 31 hospital, clinic, and cruise ship infirmary sites identified 5361 cases of ARI (including 2864 cases of ILI [53%] and 171 cases of pneumonia [3.2%]) occurring primarily in tourists and tourism workers (from 18 and 37 countries, respectively). Influenza A viruses were isolated from 41 of 210 patients with ILI at 8 of 14 land sites and 8 of 17 cruise ship infirmaries. Twenty-two influenza isolates were antigenically characterized, and all were influenza A/Sydney/05/97-like (H3N2) viruses. No other predominant pathogens were identified. We estimated that >33,000 cases of ARI might have occurred during this protracted outbreak, which was attributed primarily to influenza A/Sydney/05/97-like (H3N2) viruses. Modern travel patterns may facilitate similar outbreaks, indicating the need for increased awareness about influenza by health care providers and travelers and the desirability of year-round influenza surveillance in some regions.