Energy balance in obese, mechanically ventilated intensive care unit patients.

OBJECTIVES: The aims of this study were, first, to compare the predicted (calculated) energy requirements based on standard equations with target energy requirement based on indirect calorimetry (IC) in critically ill, obese mechanically ventilated patients; and second, to compare actual energy intake to target energy requirements. METHODS: We conducted a prospective cohort study of mechanically ventilated critically ill patients with body mass index ≥30.0 kg/m2 for whom enteral feeding was planned. Clinical and demographic data were prospectively collected. Resting energy expenditure was measured by open-circuit IC. American Society of Parenteral and Enteral Nutrition (APSPEN)/Society of Critical Care Medicine (SCCM) 2016 equations were used to determine predicted (calculated) energy requirements. Target energy requirements were set at 65% to 70% of measured resting energy expenditure as recommended by ASPEN/SCCM. Nitrogen balance was determined via simultaneous measurement of 24-h urinary nitrogen concentration and protein intake. RESULTS: Twenty-five patients (mean age: 64.5 ± 11.8 y, mean body mass index: 35.2 ± 3.6 kg/m2) underwent IC. The mean predicted energy requirement was 1227 kcal/d compared with mean measured target energy requirement of 1691 kcal/d. Predicted (calculated) energy requirements derived from ASPEN/SCCM equations were less than the target energy requirements in most cases. Actual energy intake from enteral nutrition met 57% of target energy requirements. Protein intake met 25% of target protein requirement and the mean nitrogen balance was -2.3 ± 5.1 g/d. CONCLUSIONS: Predictive equations underestimated target energy needs in this population. Further, we found that feeding to goal was often delayed resulting in failure to meet both protein and energy intake goals.

"Implications of cost-sharing for observation care among Medicare beneficiaries: a pilot survey".

BACKGROUND: Medicare beneficiaries hospitalized under observation status have significant cost-sharing responsibilities under Medicare Part B. Prior work has demonstrated an association between increased cost-sharing and health care rationing among low-income Medicare beneficiaries. The objective of this study was to explore the potential impact of observation cost-sharing on future medical decision making of Medicare beneficiaries. METHODS: Single-center pilot cohort study. A convenience sample of Medicare beneficiaries hospitalized under observation status care was surveyed. RESULTS: Out of 144 respondents, low-income beneficiaries were more likely to be concerned about the cost of their observation stay than higher-income respondents (70.7% vs29.3%, p = 0.015). If hospitalized under observation status again, there was a trend among low-income beneficiaries to request completion of their workup outside of the hospital (56.3% vs 43.8%), and to consider leaving against medical advice (AMA) (100% vs 0%), though these trends were not statistically significant (p = 0.30). CONCLUSION: The results of this pilot study suggest that low-income Medicare beneficiaries hospitalized under observation status have greater concerns about their cost-sharing obligations than their higher income peers. Cost-sharing for observation care may have unintended consequences on utilization for low-income beneficiaries. Future studies should examine this potential relationship on a larger scale.

The Unmet Need for Postacute Rehabilitation Among Medicare Observation Patients: A Single-Center Study.

BACKGROUND: Medicare beneficiaries admitted under observation status must pay for postacute inpatient rehabilitation (PAIR) services, out of pocket, at potentially prohibitive costs. OBJECTIVE: To determine if there is an unmet need for PAIR among Medicare observation patients and if this care is associated with longer hospital stay and increased rehospitalization. DESIGN/SETTING: Observational study using electronic medical record and administrative data from a regional health system. PATIENTS: 1323 community-dwelling Medicare patients admitted under observation status. MEASUREMENTS: Summary statistics were calculated for demographic and administrative variables. Physical therapy (PT) and case management recommendations for a representative sample of 386 medical records were reviewed regarding need for PAIR services. Linear regression was used to measure the association between PT recommendation and hospital length of stay, adjusting for ICD-9 (International Classification of Diseases, Ninth Revision) diagnosis, age, sex, and provider. Chi-square test was used to determine the association between PT recommendation and 30-day hospital revisit. RESULTS: Of the 1323 study patients, 11 (0.83%) were discharged to PAIR facilities. However, 17 (4.4%) of the 386 patients whose charts were reviewed received a recommendation for this care. Adjusted mean hospital stay was longer (P ⟨ 0.001) for patients recommended for rehabilitation (75.9 h) than for patients with no PT needs (46.8 h). In addition, the 30-day hospital revisit rate was higher (P = 0.037) for the patients who had been recommended for rehabilitation (52.9%, 9/17) than for those who had not (25.4%, 30/118). CONCLUSIONS: Medicare observation patients' potential need for PAIR services is 5- to 6-fold higher than their use of these services. Observation patients recommended for this care may have worse outcomes. Journal of Hospital Medicine 2017;12:168-172.

Naturally occurring human monoclonal antibodies neutralize both 1918 and 2009 pandemic influenza A (H1N1) viruses.

The 2009 pandemic influenza A (H1N1) virus exhibits hemagglutinin protein sequence homology with the 1918 pandemic influenza virus. We found that human monoclonal antibodies recognized the Sa antigenic site on the head domains of both 1918 and 2009 hemagglutinins, a site that is hypervariable due to immune selection. These antibodies exhibited high potency against the 2009 virus in vitro, and one exerted a marked therapeutic effect in vivo.

Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors.

Investigation of the human antibody response to influenza virus infection has been largely limited to serology, with relatively little analysis at the molecular level. The 1918 H1N1 influenza virus pandemic was the most severe of the modern era. Recent work has recovered the gene sequences of this unusual strain, so that the 1918 pandemic virus could be reconstituted to display its unique virulence phenotypes. However, little is known about adaptive immunity to this virus. We took advantage of the 1918 virus sequencing and the resultant production of recombinant 1918 haemagglutinin (HA) protein antigen to characterize at the clonal level neutralizing antibodies induced by natural exposure of survivors to the 1918 pandemic virus. Here we show that of the 32 individuals tested that were born in or before 1915, each showed seroreactivity with the 1918 virus, nearly 90 years after the pandemic. Seven of the eight donor samples tested had circulating B cells that secreted antibodies that bound the 1918 HA. We isolated B cells from subjects and generated five monoclonal antibodies that showed potent neutralizing activity against 1918 virus from three separate donors. These antibodies also cross-reacted with the genetically similar HA of a 1930 swine H1N1 influenza strain, but did not cross-react with HAs of more contemporary human influenza viruses. The antibody genes had an unusually high degree of somatic mutation. The antibodies bound to the 1918 HA protein with high affinity, had exceptional virus-neutralizing potency and protected mice from lethal infection. Isolation of viruses that escaped inhibition suggested that the antibodies recognize classical antigenic sites on the HA surface. Thus, these studies demonstrate that survivors of the 1918 influenza pandemic possess highly functional, virus-neutralizing antibodies to this uniquely virulent virus, and that humans can sustain circulating B memory cells to viruses for many decades after exposure-well into the tenth decade of life.

An optimized electrofusion-based protocol for generating virus-specific human monoclonal antibodies.

We sought to develop and optimize a hybridoma-based technology for generating human hybridomas that secrete virus-specific monoclonal antibodies for clinical diagnosis and therapy. We developed a novel electrofusion protocol for efficiently fusing Epstein-Barr virus (EBV)-transformed human B cells with myeloma partners. We tested seven myeloma cell lines and achieved highest efficiency when the HMMA 2.5 line was used. We optimized the electrofusion process by improving cell treatments before and after electrofusion as well as varying cell ratios, fusion medium and other experimental parameters. Our fusion efficiency increased remarkably to 0.43%, a significant improvement over the efficiency of previous PEG-based or other electrofusion methods. Using the optimized protocol, we obtained human hybridomas that secrete fully human monoclonal antibodies against two major human respiratory pathogens: respiratory syncytial virus (RSV) and an influenza H3N2 vaccine virus strain. In conclusion, we have developed an efficient and routine approach for the generation of human hybridomas secreting functional human virus-specific monoclonal antibodies.

The transmembrane domain of the respiratory syncytial virus F protein is an orientation-independent apical plasma membrane sorting sequence.

The processes that facilitate transport of integral membrane proteins though the secretory pathway and subsequently target them to particular cellular membranes are relevant to almost every field of biology. These transport processes involve integration of proteins into the membrane of the endoplasmic reticulum (ER), passage from the ER to the Golgi, and post-Golgi trafficking. The respiratory syncytial virus (RSV) fusion (F) protein is a type I integral membrane protein that is uniformly distributed on the surface of infected nonpolarized cells and localizes to the apical plasma membrane of polarized epithelial cells. We expressed wild-type or altered RSV F proteins to gain a better understanding of secretory transport and plasma membrane targeting of type I membrane proteins in polarized and nonpolarized epithelial cells. Our findings reveal a novel, orientation-independent apical plasma membrane targeting function for the transmembrane domain of the RSV F protein in polarized epithelial cells. This work provides a basis for a more complete understanding of the role of the transmembrane domain and cytoplasmic tail of viral type I integral membrane proteins in secretory transport and plasma membrane targeting in polarized and nonpolarized cells.

The human polymeric immunoglobulin receptor facilitates invasion of epithelial cells by Streptococcus pneumoniae in a strain-specific and cell type-specific manner.

Streptococcus pneumoniae is a gram-positive bacterial pathogen that causes invasive life-threatening disease worldwide. This organism also commonly colonizes the upper respiratory epithelium in an asymptomatic fashion. To invade, this pathogen must traverse the respiratory epithelial barrier, allowing it to cause disease locally or disseminate hematogenously throughout the body. Previous work has demonstrated that S. pneumoniae choline-binding protein A, a pneumococcal surface protein, interacts specifically with the human polymeric immunoglobulin receptor, which is expressed by cells in the respiratory epithelium. Choline-binding protein A is required for efficient colonization of the nasopharynx in vivo. Additionally, a recent study showed that the R6x laboratory strain of S. pneumoniae invades a human pharyngeal cell line in a human polymeric immunoglobulin receptor-dependent manner. These findings raised the possibility that the interaction between choline-binding protein A and human polymeric immunoglobulin receptor may be a key determinant of S. pneumoniae pathogenesis. However, the strain used in prior invasion studies, R6x, is an unencapsulated, nonpathogenic strain. In the present study we determined the relative ability of strain R6x or pathogenic strains to invade a variety of human polymeric immunoglobulin receptor-expressing epithelial cell lines. The results of this work suggest that human polymeric immunoglobulin receptor-dependent enhanced invasion of epithelial cells by S. pneumoniae is a limited phenomenon that occurs in a strain-specific and cell type-specific manner.