Ascertainment of Nutrition Care Process (NCP) Implementation and Use of NCP Terminologies (NCPT) among Hospital Dietitians in the Philippines.

Background and Objective: The Nutrition Care Process (NCP) is a systematic method used by dietitians to provide high-quality nutrition care resulting in good patient outcomes. This study aimed to assess the NCP implementation and use of NCP Terminologies (NCPT) among hospital dietitians in the Philippines. Specifically, the study aimed at assessing the knowledge, perception, and practices on NCP and use of NCPT and correlate them with the dietitians' education, and professional and employment profile; and explain the barriers and facilitators of the practice of NCP and use of NCPT among hospital dietitians in the Philippines. Methods: The knowledge, perception, and practices (KPP) on NCP and NCPT of the dietitians employed in the Philippine Department of Health's licensed level 3 hospitals were determined using a validated questionnaire. Significant factors associated with the KPP were also determined. The barriers and facilitators of the practice of NCP and NCPT were determined using focus group discussion and key informant interviews of chief clinical dietitians and hospital administrators, respectively. Results: The study revealed that majority of the participants had a high level of knowledge on NCP and NCPT, positively perceived its implementation, and more than half of them implement NCP and NCPT in the hospitals. The participants' knowledge on NCP and NCPT was significantly associated with research involvement and active membership in a professional organization. While the practice of NCP and NCPT was significantly associated with having NCP-related trainings, frequency of trainings, and active membership in a professional organization. The barriers to NCP implementation were insufficient resources; lack of orientation, trainings, and support; organizational and administrative constraints; pandemic constraints; insufficient time; and lack of confidence to conduct NCP. While the facilitators of implementation were collaboration, dedication, and commitment of the healthcare team; institutionalization of NCP laws and policies; budget allocation for NCP-related activities; monitoring and consistency of NCP implementation; and work schedule. Conclusion: The findings suggest that the implementation of NCP and NCPT in the Philippines needs further support from the institution, professional organizations, and policy makers by developing strategies to cope with the barriers, and strengthen the facilitators and factors associated with practice.

Plasma metabolomics changes comparing daytime to overnight infusions of home parenteral nutrition in adult patients with short bowel syndrome: Secondary analysis of a clinical trial.

BACKGROUND: Home parenteral nutrition (HPN) is often cycled nocturnally and is expected to result in glucose intolerance and sleep disruption partly due to circadian misalignment. This study aimed to define the metabolic response when HPN is cycled during the daytime compared to overnight. METHODS: This secondary analysis leveraged samples from a clinical trial in adults with short bowel syndrome consuming HPN (ClinicalTrials.gov: NCT04743960). Enrolled patients received 1 week of HPN overnight followed by 1 week of HPN during the daytime. Fasting blood samples were collected following each study period and global metabolic profiles were examined from plasma samples. Differential metabolite abundance was determined from normalized and scaled data using adjusted Linear Models for MicroArray Data models followed by pathway enrichment analysis. RESULTS: Nine patients (mean age, 52.6 years; 78% female; mean BMI 20.7 kg/m2) provided samples. Among 622 identified metabolites, changes were observed in 36 metabolites at Punadj < 0.05 with higher abundance of fatty acids, long-chain and polyunsaturated fatty acids (Dihomo-gamma-linolenic acid, arachidonate (20:4n6), docosahexaenoate (DHA; 22:6n3)) and glycerolipids with daytime infusions. Enrichment analysis identified changes in pathways related to the biosynthesis of unsaturated fatty acids, d-arginine, and d-ornithine metabolism, and linoleic acid metabolism (Punadj<0.05). CONCLUSION: Daytime infusions of HPN may result in changes in circulating lipids and amino acid composing metabolic pathways previously implicated in circadian rhythms. As this is the first untargeted metabolomics study of HPN, larger studies are needed.

Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation.

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies. Here we used 278 bronchoalveolar lavage (BAL) fluid samples to study the lung microenvironment in 229 pediatric patients who have undergone HCT treated at 32 children's hospitals between 2014 and 2022. By leveraging paired microbiome and human gene expression data, we identified high-risk BAL compositions associated with in-hospital mortality (P = 0.007). Disadvantageous profiles included bacterial overgrowth with neutrophilic inflammation, microbiome contraction with epithelial fibroproliferation and profound commensal depletion with viral and staphylococcal enrichment, lymphocytic activation and cellular injury, and were replicated in an independent cohort from the Netherlands (P = 0.022). In addition, a broad array of previously occult pathogens was identified, as well as a strong link between antibiotic exposure, commensal bacterial depletion and enrichment of viruses and fungi. Together these lung-immune system-microorganism interactions clarify the important drivers of fatal lung injury in pediatric patients who have undergone HCT. Further investigation is needed to determine how personalized interpretation of heterogeneous pulmonary microenvironments may be used to improve pediatric HCT outcomes.

Polyvascular disease is common in patients undergoing carotid endarterectomy and lower extremity bypass and is associated with worse outcomes.

BACKGROUND: Polyvascular disease is strongly associated with increased risk of cardiovascular morbidity and mortality. However, its prevalence in patients undergoing carotid and lower extremity surgical revascularization and its impact on outcomes are unknown. METHODS: The Vascular Quality Initiative was queried for carotid endarterectomy (CEA) or infrainguinal lower extremity bypass (LEB), 2013-2019. Polyvascular disease was defined as presence of atherosclerotic occlusive disease in more than one arterial bed: carotid, coronary, and infrainguinal. Primary outcomes were (1) composite perioperative myocardial infarction (MI) or death and (2) 5-year survival. Patient characteristics and perioperative outcomes were evaluated using the χ2 test and multivariable logistic regression. Survival was analyzed using Kaplan-Meier method and Cox proportional hazards multivariable models. RESULTS: Polyvascular disease was identified in 47% of CEA (39.0% in 2 arterial beds, 7.6% in 3 arterial beds; n = 93,736) and 47% of LEB (41.0% in 2 arterial beds, 5.7% in 3 arterial beds; n = 25,223). For both CEA and LEB, patients with polyvascular disease had more comorbidities including hypertension, congestive heart disease, chronic obstructive pulmonary disease, smoking, diabetes mellitus, and end-stage renal disease (P < .0001). Perioperative MI/death rates increased with increasing number of vascular beds affected following CEA (0.9% in 1 bed vs 1.5% in 2 beds vs 2.7% in 3 beds; P < .001) and LEB (2.2% in 1 bed vs 5.3% in 2 beds vs 6.6% in 3 beds; P < .001). Polyvascular disease was associated independently with perioperative MI/death after CEA (odds ratio, 1.59; 95% confidence interval [CI], 1.40-1.81;P < .0001) and LEB (odds ratio, 1.78; 95% CI, 1.52-2.08; P < .0001). Five-year survival was decreased in patients with polyvascular disease after CEA (82% in 3 beds vs 88% in 2 beds vs 92% in 1 bed; P < .01) and LEB (72% in 3 beds vs 75% in 2 beds vs 84% in 1 bed; P < .01) in a dose-dependent manner, with the lowest 5-year survival observed in those with three arterial beds involved. Polyvascular disease was independently associated with 5-year mortality after CEA (hazard ratio, 1.33; 95% CI, 1.24-1.40; P = .0001) and LEB (hazard ratio, 1.30; 95% CI, 1.20-1.41; P = .0001). CONCLUSIONS: Polyvascular disease is common in patients undergoing CEA and LEB and is associated with a higher risk of perioperative MI/death and decreased long-term survival. After revascularization, patients with polyvascular disease should be considered for more aggressive cardioprotective medications and closer follow-up.

The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection.

SARS-CoV-2 infection can cause severe pneumonia, wherein exacerbated inflammation plays a major role. This is reminiscent of the process commonly termed cytokine storm, a condition dependent on a disproportionated production of cytokines. This state involves the activation of the innate immune response by viral patterns and coincides with the biosynthesis of the biomass required for viral replication, which may overwhelm the capacity of the endoplasmic reticulum and drive the unfolded protein response (UPR). The UPR is a signal transduction pathway composed of three branches that is initiated by a set of sensors: inositol-requiring protein 1 (IRE1), protein kinase RNA-like ER kinase (PERK), and activating transcription factor 6 (ATF6). These sensors control adaptive processes, including the transcriptional regulation of proinflammatory cytokines. Based on this background, the role of the UPR in SARS-CoV-2 replication and the ensuing inflammatory response was investigated using in vivo and in vitro models of infection. Mice and Syrian hamsters infected with SARS-CoV-2 showed a sole activation of the Ire1α-Xbp1 arm of the UPR associated with a robust production of proinflammatory cytokines. Human lung epithelial cells showed the dependence of viral replication on the expression of UPR-target proteins branching on the IRE1α-XBP1 arm and to a lower extent on the PERK route. Likewise, activation of the IRE1α-XBP1 branch by Spike (S) proteins from different variants of concern was a uniform finding. These results show that the IRE1α-XBP1 system enhances viral replication and cytokine expression and may represent a potential therapeutic target in SARS-CoV-2 severe pneumonia.

Diagnostic accuracy of tongue swab testing on two automated tuberculosis diagnostic platforms, Cepheid Xpert MTB/RIF Ultra and Molbio Truenat MTB Ultima.

Tongue dorsum swabbing is a potential alternative to sputum collection for tuberculosis (TB) testing. Previous studies showed that Cepheid Xpert MTB/RIF Ultra (Xpert Ultra) can detect Mycobacterium tuberculosis DNA on tongue swabs stored in buffer, with 72% sensitivity and 100% specificity relative to a sputum microbiological reference standard (sputum MRS). The present study evaluated a more convenient sample collection protocol (dry swab storage), combined with streamlined sample processing protocols, for evaluating two commercial TB diagnostic tests: Xpert Ultra and Molbio Truenat MTB Ultima (MTB Ultima). Copan FLOQSwabs were self-collected or collected by study workers from 321 participants in Western Cape, South Africa. All participants had symptoms suggestive of TB, and 245 of them had sputum MRS-confirmed TB (by sputum MGIT culture and/or Xpert Ultra). One tongue swab per participant was tested on Xpert Ultra, and another tongue swab was tested with MTB Ultima. Xpert Ultra was 75.5% sensitive and 100% specific relative to sputum MRS, similar to previous methods that used swabs stored in buffer. MTB Ultima was 71.6% sensitive and 96.9% specific relative to sputum MRS. When sample lysates that were false-negative or invalid by MTB Ultima were frozen, thawed, and re-tested, MTB Ultima sensitivity rose to 79.1%. Both tests were more sensitive with swabs from participants with higher sputum Xpert Ultra semi-quantitative results. Although additional development could improve diagnostic accuracy, these results further support tongue swabs as easy-to-collect samples for TB testing. IMPORTANCE: Tongue dorsum swabbing is a promising alternative to sputum collection for tuberculosis (TB) testing. Our results lend further support for tongue swabs as exceptionally easy-to-collect samples for high-throughput TB testing.

Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable, with 99% overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.

Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition: A modified Delphi approach.

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the etiologic criterion for inflammation. METHODS: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified-Delphi review. A multi-round review and revision process served to develop seven guidance statements. RESULTS: The final round of review was highly favorable with 99 % overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (mg/dL or mg/L) for the clinical laboratory that is being used. CONCLUSION: Confirmation of inflammation should be guided by clinical judgement based upon underlying diagnosis or condition, clinical signs, or CRP.

Glycemic and sleep effects of daytime compared with those of overnight infusions of home parenteral nutrition in adults with short bowel syndrome: A quasi-experimental pilot trial.

BACKGROUND: Patients with short bowel syndrome (SBS) dependent on home parenteral nutrition (HPN) commonly cycle infusions overnight, likely contributing to circadian misalignment and sleep disruption. METHODS: The objective of this quasi-experimental, single-arm, controlled, pilot trial was to examine the feasibility, safety, and efficacy of daytime infusions of HPN in adults with SBS without diabetes. Enrolled patients were fitted with a continuous glucose monitor and wrist actigraph and were instructed to cycle their infusions overnight for 1 wk, followed by daytime for another week. The 24-h average blood glucose, the time spent >140 mg/dL or <70 mg/dL, and sleep fragmentation were derived for each week and compared using Wilcoxon signed-rank test. Patient-reported quality-of-life outcomes were also compared between the weeks. RESULTS: Twenty patients (mean age, 51.7 y; 75% female; mean body mass index, 21.5 kg/m2) completed the trial. Overnight infusions started at 21:00 and daytime infusions at 09:00. No serious adverse events were noted. There were no differences in 24-h glycemia (daytime-median: 93.00 mg/dL; 95% CI: 87.7-99.9 mg/dL, compared with overnight-median: 91.1 mg/dL; 95% CI: 89.6-99.0 mg/dL; P = 0.922). During the day hours (09:00-21:00), the mean glucose concentrations were 13.5 (5.7-22.0) mg/dL higher, and the time spent <70 mg/dL was 15.0 (-170.0, 22.5) min lower with daytime than with overnight HPN. Conversely, during the night hours (21:00-09:00), the glucose concentrations were 16.6 (-23.1, -2.2) mg/dL lower with daytime than with overnight HPN. There were no differences in actigraphy-derived measures of sleep and activity rhythms; however, sleep timing was later, and light at night exposure was lower with daytime than with overnight HPN. Patients reported less sleep disruptions due to urination and fewer episodes of uncontrollable diarrhea or ostomy output with daytime HPN. CONCLUSIONS: Daytime HPN was feasible and safe in adults with SBS and, compared with overnight HPN, improved subjective sleep without increasing 24-h glucose concentrations. This trial was registered at clinicaltrials.gov as NCT04743960 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT04743960).

Concomitant use of monoamine oxidase inhibitor and tyrosine in parenteral nutrition.

Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of tyramine in the body, and can cause a sudden increase in blood pressure with significant tyramine build up. This phenomenon, when it occurs, is known as tyramine pressor response. It is unknown if tyrosine administered in parenteral nutrition (PN) leads to tyramine build-up with concomitant use of MAOIs. It is also unknown if PN patients who are taking MAOI are at risk for the tyramine pressor response. This is a theoretical possibility as tyrosine endogenously undergoes decarboxylation to produce tyramine. We describe our experience with a 67-year-old woman with severe depression who was on the MAOI, transdermal selegiline. Her clinical course was complicated by an inability to take adequate per oral (PO) intake and she met criteria for unspecified severe protein-calorie-malnutrition in the context of social or environmental circumstances. Therefore, she required PN initiation. PlenamineTM (B. Braun, Bethlehem, PA, USA) was used as the amino acid source in the PN, which contains 39 mg of tyrosine per 100 ml of solution. The patient was monitored closely for any signs of hypertensive crisis while on PN and selegiline. She safely tolerated the combined therapy without any side effects. This is the first documented report of co-administration of PN containing tyrosine along with a MAOI. Our findings suggest that the dose of selegiline used in this patient can be co-administered safely in the setting of PN. However, further study is needed to verify our findings beyond this one patient. In conclusion, we recommend initiating PN and increasing it to goal in patients taking MAOIs, gradually, while monitoring for hypertensive crisis given the theoretical possibility of the tyramine pressor response.

A Call to Action: Using Curriculum Mapping at Four Medical Schools in Massachusetts to Advance Serious Illness Communication Training in Undergraduate Medical Education.

Background: Practicing physicians require serious illness communication (SIC) skills to ensure high-quality, humanistic care for patients and families as they face life-changing medical decisions. However, a majority of U.S. medical schools do not require formal training in SIC and fail to provide students deliberate practice before graduation. The Massachusetts Medical Schools' Collaborative was created to ensure that students receive foundational SIC training in undergraduate medical education. This Collaborative developed a curriculum-mapping tool to assess SIC at four medical schools. Objective: We aimed to understand existing educational activities across four medical schools and identify opportunities to build longitudinal, developmentally based curricular threads in SIC. Design: From July 2019 to April 2021, faculty, staff, and medical students assessed current educational activities related to five core competencies in SIC, adapted for students from national competencies for palliative medicine fellows, using a curriculum mapping tool. Measurements: The group selected 23 keywords and collected metrics to describe the timing, instruction and assessment for each school's educational activities. Results: On average, there were only 40 hours of required curricula in SIC over four years. Over 80% of relevant SIC hours occurred as elective experiences, mostly during the postclerkship phase, with limited capacity in these elective experiences. Only one school had SIC educational activities during the clerkship phase when students are developing clinical competencies. Assessment methods focused on student participation, and no school-assessed clinical performance in the clerkship or postclerkship phase. Conclusions: Medical schools are failing to consistently train and ensure basic competency in effective, compassionate SIC. Curriculum mapping allows schools to evaluate their current state on a particular topic such as SIC, ensure proper assessment, and evaluate curricular changes over time. Through the deliberate inclusion of SIC competencies in longitudinal curriculum design, we can fill this training gap and create best practices in undergraduate medical education.

Associations of sleep duration and daytime sleepiness with plasma amyloid beta and cognitive performance in cognitively unimpaired, middle-aged and older African Americans.

STUDY OBJECTIVES: Given the established racial disparities in both sleep health and dementia risk for African American populations, we assess cross-sectional and longitudinal associations of self-report sleep duration (SRSD) and daytime sleepiness with plasma amyloid beta (Aß) and cognition in an African American (AA) cohort. METHODS: In a cognitively unimpaired sample drawn from the African Americans Fighting Alzheimer's in Midlife (AA-FAiM) study, data on SRSD, Epworth Sleepiness Scale, demographics, and cognitive performance were analyzed. Aß40, Aß42, and the Aß42/40 ratio were quantified from plasma samples. Cross-sectional analyses explored associations between baseline predictors and outcome measures. Linear mixed-effect regression models estimated associations of SRSD and daytime sleepiness with plasma Aß and cognitive performance levels and change over time. RESULTS: One hundred and forty-seven participants comprised the cross-sectional sample. Baseline age was 63.2 ±â€…8.51 years. 69.6% self-identified as female. SRSD was 6.4 ±â€…1.1 hours and 22.4% reported excessive daytime sleepiness. The longitudinal dataset included 57 participants. In fully adjusted models, neither SRSD nor daytime sleepiness is associated with cross-sectional or longitudinal Aß. Associations with level and trajectory of cognitive test performance varied by measure of sleep health. CONCLUSIONS: SRSD was below National Sleep Foundation recommendations and daytime sleepiness was prevalent in this cohort. In the absence of observed associations with plasma Aß, poorer self-reported sleep health broadly predicted poorer cognitive function but not accelerated decline. Future research is necessary to understand and address modifiable sleep mechanisms as they relate to cognitive aging in AA at disproportionate risk for dementia. CLINICAL TRIAL INFORMATION: Not applicable.

Molecular detection of pre-ribosomal RNAs of Mycobacterium bovis bacille Calmette-Guérin and Mycobacterium tuberculosis to enhance pre-clinical tuberculosis drug and vaccine development.

Efforts are underway globally to develop effective vaccines and drugs against M. tuberculosis (Mtb) to reduce the morbidity and mortality of tuberculosis. Improving detection of slow-growing mycobacteria could simplify and accelerate efficacy studies of vaccines and drugs in animal models and human clinical trials. Here, a real-time reverse transcription PCR (RT-PCR) assay was developed to detect pre-ribosomal RNA (pre-rRNA) of Mycobacterium bovis bacille Calmette-Guérin (BCG) and Mtb. This pre-rRNA biomarker is indicative of bacterial viability. In two different mouse models, the presence of pre-rRNA from BCG and Mtb in ex vivo tissues showed excellent agreement with slower culture-based colony-forming unit assays. The addition of a brief nutritional stimulation prior to molecular viability testing further differentiated viable but dormant mycobacteria from dead mycobacteria. This research has set the stage to evaluate pre-rRNA as a BCG and/or Mtb infection biomarker in future drug and vaccine clinical studies.

Ascertainment of Nutrition Care Process (NCP)Implementation and Use of NCP Terminologies (NCPT) among Hospital Dietitians in the Philippines

Background and Objective@#The Nutrition Care Process (NCP) is a systematic method used by dietitians to provide high-quality nutrition care resulting in good patient outcomes. This study aimed to assess the NCP implementation and use of NCP Terminologies (NCPT) among hospital dietitians in the Philippines. Specifically, the study aimed at assessing the knowledge, perception, and practices on NCP and use of NCPT and correlate them with the dietitians' education, and professional and employment profile; and explain the barriers and facilitators of the practice of NCP and use of NCPT among hospital dietitians in the Philippines. @*Methods@#The knowledge, perception, and practices (KPP) on NCP and NCPT of the dietitians employed in the Philippine Department of Health’s licensed level 3 hospitals were determined using a validated questionnaire. Significant factors associated with the KPP were also determined. The barriers and facilitators of the practice of NCP and NCPT were determined using focus group discussion and key informant interviews of chief clinical dietitians and hospital administrators, respectively. @*Results@#The study revealed that majority of the participants had a high level of knowledge on NCP and NCPT, positively perceived its implementation, and more than half of them implement NCP and NCPT in the hospitals. The participants’ knowledge on NCP and NCPT was significantly associated with research involvement and active membership in a professional organization. While the practice of NCP and NCPT was significantly associated with having NCP-related trainings, frequency of trainings, and active membership in a professional organization. The barriers to NCP implementation were insufficient resources; lack of orientation, trainings, and support; organizational and administrative constraints; pandemic constraints; insufficient time; and lack of confidence to conduct NCP. While the facilitators of implementation were collaboration, dedication, and commitment of the healthcare team; institutionalization of NCP laws and policies; budget allocation for NCP-related activities; monitoring and consistency of NCP implementation; and work schedule. @*Conclusion@#The findings suggest that the implementation of NCP and NCPT in the Philippines needs further support from the institution, professional organizations, and policy makers by developing strategies to cope with the barriers, and strengthen the facilitators and factors associated with practice.

Pulmonary microbiome and transcriptome signatures reveal distinct pathobiologic states associated with mortality in two cohorts of pediatric stem cell transplant patients.

Lung injury is a major determinant of survival after pediatric hematopoietic cell transplantation (HCT). A deeper understanding of the relationship between pulmonary microbes, immunity, and the lung epithelium is needed to improve outcomes. In this multicenter study, we collected 278 bronchoalveolar lavage (BAL) samples from 229 patients treated at 32 children's hospitals between 2014-2022. Using paired metatranscriptomes and human gene expression data, we identified 4 patient clusters with varying BAL composition. Among those requiring respiratory support prior to sampling, in-hospital mortality varied from 22-60% depending on the cluster (p=0.007). The most common patient subtype, Cluster 1, showed a moderate quantity and high diversity of commensal microbes with robust metabolic activity, low rates of infection, gene expression indicating alveolar macrophage predominance, and low mortality. The second most common cluster showed a very high burden of airway microbes, gene expression enriched for neutrophil signaling, frequent bacterial infections, and moderate mortality. Cluster 3 showed significant depletion of commensal microbes, a loss of biodiversity, gene expression indicative of fibroproliferative pathways, increased viral and fungal pathogens, and high mortality. Finally, Cluster 4 showed profound microbiome depletion with enrichment of Staphylococci and viruses, gene expression driven by lymphocyte activation and cellular injury, and the highest mortality. BAL clusters were modeled with a random forest classifier and reproduced in a geographically distinct validation cohort of 57 patients from The Netherlands, recapitulating similar cluster-based mortality differences (p=0.022). Degree of antibiotic exposure was strongly associated with depletion of BAL microbes and enrichment of fungi. Potential pathogens were parsed from all detected microbes by analyzing each BAL microbe relative to the overall microbiome composition, which yielded increased sensitivity for numerous previously occult pathogens. These findings support personalized interpretation of the pulmonary microenvironment in pediatric HCT, which may facilitate biology-targeted interventions to improve outcomes.

Characteristics and outcomes of children, adolescents and young adults with relapsed/refractory non-hodgkin lymphoma undergoing autologous stem cell transplant.

BACKGROUND: There is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). METHODS: Patients aged 0-39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed. RESULTS: Two hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6-39) years. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) (44%), T-NHL (19%) and primary mediastinal B-Cell lymphoma (PMBCL) (19%). Younger patients (age ≤ 25) had lower incidence of DLBCL and higher incidence of PMBCL and T-NHL compared to older patients (age > 25) (P = 0.02). None of the younger patients had double hit (DH)/double expressor (DE) DLBCL, compared to 14 patients in the older age group (18%, P = 0.07). Considering the three main aggressive NHL subtypes (DLBCL, PMBCL and T-NHL), younger patients had numerically better 15-year post-transplant progression free survival (PFS) (67% vs. 54%) and overall survival (OS) (71% vs. 62%) compared to older patients, yet these differences did not reach statistical significance (P = 0.19 and P = 0.24, respectively). In multivariate analysis, not achieving a CR prior to ASCT was independently predictive of worse PFS [partial remission (PR) (HR, 3.9); stable disease (SD) (HR, 18.0), P = 0.03] and of worse OS [PR (HR, 4.2), SD (HR, 6.5) and progressive disease (HR, 4.7), P < 0.0001]. DH/DE status was an independent adverse predictor of PFS in multivariate analysis (HR 5.8, p = 0.03). Ten patients (4.5%) (all aged > 25 years) developed second primary malignancies (SPM), at a median of 34.4 (range, 1.0-196.6) months after ASCT, and SPM was the cause of death in five (50%) of them. CONCLUSIONS: CAYA NHL patients aged ≤ 25 years who received ASCT presented a distinct NHL histology as compared to older CAYA patients, and none in this younger age group had DH/DE DLBCL. We observed a trend towards improved PFS and OS in younger patients. Disease status at ASCT was predictive of both PFS and OS. DH/DE status was an adverse predictor of PFS.

Synthesis, Structure, and Photophysical Properties of Platinum Compounds with Thiophene-Derived Cyclohexyl Diimine Ligands.

Platinum(II) and platinum(IV) compounds were prepared by the stereoselective and regioselective reactions of thiophene-derived cyclohexyl diimine C^N^N-ligands with [Pt2Me4(µ-SMe2)2]. Newly synthesized ligands were characterized by NMR spectroscopy and elemental analysis, and Pt(II)/Pt(IV) compounds were characterized by NMR spectroscopy, elemental analysis, high-resolution mass spectrometry, and single-crystal X-ray diffraction. UV-vis absorbance and photoluminescence measurements were performed on newly synthesized complexes, as well as structurally related Pt(II)/Pt(IV) compounds with benzene-derived cyclohexyl diimine ligands, in dichloromethane solution, as solids, and as 5% by weight PMMA-doped films. DFT and TD-DFT calculations were performed, and the results were compared with the observed spectroscopic properties of the newly synthesized complexes. X-ray total scattering measurements and real space pair distribution function analysis were performed on the synthesized complexes to examine the local- and intermediate-range atomic structures of the emissive solid states.

Tongue swab testing on two automated tuberculosis diagnostic platforms, Cepheid Xpert® MTB/RIF Ultra and Molbio Truenat® MTB Ultima.

Tongue dorsum swabbing is a potential alternative to sputum collection for tuberculosis (TB) testing. Previous studies showed that Cepheid Xpert® MTB/RIF Ultra (Xpert Ultra) can detect Mycobacterium tuberculosis (MTB) DNA in tongue swabs stored in buffer, with 72% sensitivity and 100% specificity relative to a sputum microbiological reference standard (sputum MRS). The present study evaluated a more convenient sample collection protocol (dry swab storage), combined with streamlined sample processing protocols, for side-by-side analysis using two commercial TB diagnostic tests: Xpert Ultra and Molbio Truenat® MTB Ultima (MTB Ultima). Copan FLOQSwabs were self-collected, or collected by study workers, from 321 participants in Western Cape, South Africa. All participants had symptoms suggestive of TB, and 245 of them had sputum MRS-confirmed TB (by sputum culture and/or Xpert Ultra). One tongue swab per participant was tested on Xpert Ultra and another tongue swab was tested with MTB Ultima. Xpert Ultra was 75.4% sensitive and 100% specific, and MTB Ultima was 71.6% sensitive and 96.9% specific, relative to sputum MRS. When sample lysates that were false-negative by MTB Ultima were frozen, thawed, and re-tested, MTB Ultima sensitivity rose to 79.1%. Both tests were more sensitive with swabs from participants with higher sputum Xpert semi-quantitative results. The protocol for Xpert Ultra enabled fast and easy testing of dry-stored swabs with no loss of accuracy relative to previous methods. MTB Ultima testing of dry-stored swabs exhibited comparable performance to Xpert Ultra. These results further support tongue swabs as easy-to-collect samples for high-throughput TB testing.