Nasal Mucosal Cytokines as Potential Biomarkers for Assessing Disease Severity and Class of Pathogen in Children with Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in children. Assessing disease severity and etiology remains challenging in the clinical setting. The objective of this study was to identify mucosal biomarkers that could potentially assist with patient classification. METHODS: We analyzed mucosal concentrations of cytokines in nasopharyngeal samples obtained from a convenience sample of 182 children with CAP and 26 matched healthy controls. Pathogens were identified by cultures and molecular assays. Severe disease was defined by hospital stay ≥ 3 days, and/or PICU admission. Data were analyzed according to identified pathogens and disease severity. RESULTS: Children with CAP and detected atypical bacteria had significantly higher concentrations of MCP-2, IFN-γ and CXCL10 among others compared with those with typical bacteria. Children with influenza virus had significantly higher concentrations of MCP-2, CXCL10, CXCL11, CX3CL1, and IFN-γ than those with typical bacteria. Additionally, children with severe CAP had significantly higher concentrations of CCL23 than children with mild/moderate disease, irrespective of the pathogen(s) identified. CONCLUSIONS: We identified differences in mucosal concentrations of inflammatory and antiviral cytokines in children with CAP according to disease severity and detected pathogens. Mucosal biomarkers represent a promising approach to help assessing disease severity and etiology.

Outcomes among Patients with End-Stage Kidney Disease and Chronic Limb-Threatening Ischemia: A Population-based Cohort Study.

OBJECTIVE: To understand mortality and secondary outcomes in patients with both end-stage kidney disease (ESKD) and chronic limb-threatening ischemia (CLTI) after no procedural treatment, primary amputation, endovascular treatment, and open surgery. SUMMARY BACKGROUND DATA: ESKD and CLTI commonly cooccur and limited prior work has demonstrated poor outcomes including one-year survival despite treatment. METHODS: We conducted a retrospective national cohort study of United States Renal Data System data from January 1, 2016 to December 31, 2019 to determine mortality, major postoperative complications, and other outcomes. We performed an exploratory analysis comparing two-year survival by treatment using propensity matching. RESULTS: Of 1,876,652 records with a CLTI diagnosis, we identified 3,908 patients with ESKD and an incident CLTI diagnosis. Mean age at CLTI diagnosis was 65.7 years and 2,405 (61.5%) were male. 2,696 (69.0%) had no procedural treatment, 609 (15.6%) had major limb amputation, 439 (11.2%) had endovascular treatment, and 164 (4.2%) had open surgery. There was 44.9% mortality at one year, along with 41.8% major postoperative complications and 52.6% readmissions at 90 days. Comparing two-year survival, we found no differences between the amputation and endovascular cohorts (P=0.08) and between endovascular and open (P=.06). There was superior two-year survival in the open surgery cohort compared to the amputation cohort (P=0.002). CONCLUSIONS: Patients living with both ESKD and CLTI experience poor outcomes irrespective of treatment. Exploratory analyses demonstrated that two-year survival among the three principal procedural treatments was similar except for superior survival among patients undergoing open therapy compared to primary amputation.

Asymptomatic Carotid Artery Stenosis, Cognitive Function, and the Impact of Carotid Revascularization: A Narrative Review.

BACKGROUND: The association between asymptomatic carotid artery stenosis and impaired cognition, and the cognitive changes after revascularization remain active areas of interest in the field of carotid disease. This narrative review focuses on the association between carotid artery atherosclerosis and impaired cognitive function, proposed mechanisms, and the effects of carotid revascularization on cognition. METHODS: A critical review of the literature to identify studies evaluating carotid artery stenosis, cognition, and carotid revascularization was performed using PubMed to query the MEDLINE database through March 2023. RESULTS: Many studies demonstrate a link between carotid disease and cognitive impairment but direct evidence is lacking. Revascularization may offer cognitive benefits but the effect is likely subtle and affected by the choice of revascularization procedure. CONCLUSIONS: Integrating cognitive outcomes into ongoing randomized controlled trials such as the nested CREST-H arm of the CREST-2 trial hold promise for offering new insight into the role of carotid artery stenosis and carotid revascularization on cognition.

Implementation of routine HIV testing policy in medical admissions in the sultanate of Oman: An experience from the Middle East.

OBJECTIVES: To tackle the issue of late HIV diagnosis in the country, the Ministry of Health (MOH) in Oman introduced a national policy of routine opt-out HIV in medical admission units in September 2022. We hereby report the implementation and outcomes of this policy. METHOD: All patients aged 16-65 years admitted to a medical ward in secondary and local hospitals were offered an HIV test regardless of their symptoms by medical doctors, with training and support from HIV teams. A retrospective review for the period from September 2022 to September 2023 was conducted to determine the HIV testing rate and outcomes of those testing HIV seropositive. RESULT: Over 12 months, there were 23,399 admissions; 6889 had HIV tests. Thirty-two patients (0.46 %) were diagnosed with HIV; all of them were new diagnoses. Two cases were diagnosed during seroconversion. 12 cases had AIDS-defining illnesses. Four contacts were tested HIV positive. Twenty-five out of 28 alive patients are on ART. CONCLUSION: This is the first national policy of a routine opt-out HIV in medical admission units in the MENA region. Our experience showed that, even in low HIV prevalence and high HIV stigma settings, this policy is feasible, acceptable, and effective.

Standardized therapies after ECMO program (STEP); a novel approach to pediatric post-ECMO care.

BACKGROUND: The study objective was to characterize compliance with Standardized Therapy after ECMO Program (STEP), an intentional discharge pathway for extracorporeal membrane oxygenation (ECMO) survivors in a US pediatric hospital. METHODS: The program identified pediatric ECMO survivors before discharge, appropriate consultations were reviewed and requested, families were educated on ECMO sequelae, and ECMO summaries were sent to pediatricians. Compliance with institutional post-ECMO guidelines was evaluated before and after STEP implementation. RESULTS: We identified 77 ECMO survivors to hospital discharge (36 [46.8%] before and 41 [53.2%] after STEP implementation). There was a significant increase in complete (38.8% vs. 74.2%, p < 0.001) and time-appropriate neurodevelopmental testing (71.4% vs. 95.6%, p = 0.03). Significant increase in inpatient evaluations by neurology (52.7% vs. 75.6%, p = 0.03) and audiology (66.7% vs. 87.8%, p = 0.02), and in referrals for outpatient audiology (66.6 vs. 95.1%, p = 0.002), physical therapy (P.T.) (63.8% vs. 95.1%, p = 0.001), occupational therapy (O.T.) (63.8% vs. 95.1%, p = 0.001) and speech-language pathology (S.L.P.) (55.5% vs. 95.1%, p < 0.001) were noted. CONCLUSION: Implementing an intentional discharge pathway for pediatric ECMO survivors (STEP) successfully increases inpatient and outpatient compliance with hospital and Extracorporeal life support organization (ELSO) follow-up guidelines. It leads to timely and complete neurodevelopmental evaluation.

Patients with dementia or frailty undergoing major limb amputation have poor outcomes.

OBJECTIVE: Major lower limb amputation is a disfiguring operation associated with impaired mobility and high near-term mortality. Informed decision-making regarding amputation requires outcomes data. Despite the co-occurrence of both chronic limb-threatening ischemia (CLTI) and Alzheimer's disease and related dementias (ADRD), there is sparse data on the outcomes of major limb amputation in this population and the impact of frailty. We sought to determine mortality, complications, readmissions, revisions, intensive interventions (eg, cardiopulmonary resuscitation), and other outcomes after amputation for CLTI in patients living with ADRD looking at the modifying effects of frailty. METHODS: We examined Medicare fee-for-service claims data from January 1, 2016, to December 31, 2020. Patients with CLTI undergoing amputation at or proximal to the ankle were included. Along with demographic information, dementia status, and comorbid conditions, we measured frailty using a claims-based frailty index. We dichotomized dementia and frailty (pre-frail/robust = "non-frail" vs moderate/severe frailty = "frail") to create four groups: non-frail/non-ADRD, frail/non-ADRD, non-frail/ADRD, and frail/ADRD. We used linear and logistic regression via generalized estimating equations in addition to performing selected outcomes analyses with death as a competing risk to understand the association between dementia status, frailty status, and 1-year mortality as our primary outcome in addition to the postoperative outcomes outlined above. RESULTS: Among 46,930 patients undergoing major limb amputation, 11,465 (24.4%) had ADRD and 24,790 (52.8%) had frailty. Overall, 55.9% of amputations were below-knee. Selected outcomes among frail/ADRD patients undergoing amputation (n = 10,153) were: 55.3% 1-year mortality 29.6% readmissions at 30 days, and 32.3% amputation revision/reoperation within 1 year. Of all four groups, those in the frail/ADRD had the worst outcomes only for 1-year mortality. CONCLUSIONS: First, patients with ADRD or moderate/severe frailty suffer an array of very poor outcomes after major limb amputation for CLTI, including high mortality, readmissions, revision, and risks of discharge to higher levels of care. Second, there is a complex relationship between outcome severity and ADRD/frailty status. Specifically, frailty is more often than ADRD associated with the poorest results for any given outcome. These data provide important outcomes data to help align decision-making with health care values and goals.

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In this narrative medicine essay, a pediatric infectious disease physician relates how he has learned to understand the protective role of code-shifting in his life and how that understanding has aided him in promoting an inclusive environment in academic medicine.

Racial and Gender Differences in Cardiorespiratory Fitness and Atrial Fibrillation.

The expanding field of cardiorespiratory fitness (CRF) in individuals with and without atrial fibrillation (AF) presents a complex landscape, demanding careful interpretation of the existing research. AF, characterized by significant mortality and morbidity, prompts the exploration of strategies to mitigate its impact. Increasing physical activity (PA) levels emerges as a promising avenue to address AF risk factors, such as obesity, hypertension, and diabetes mellitus, through mechanisms of reduced vasoconstriction, endothelin-1 modulation, and improved insulin sensitivity. However, caution is warranted, as recent investigations suggest a heightened incidence of AF, particularly in athletes engaged in high-intensity exercise, due to the formation of ectopic foci and changes in cardiac anatomy. Accordingly, patients should adhere to guideline-recommended amounts of low-to-moderate PA to balance benefits and minimize adverse effects. When looking closer at the current evidence, gender-specific differences have been observed and challenged conventional understanding, with women demonstrating decreased AF risk even at extreme exercise levels. This phenomenon may be rooted in divergent hemodynamic and structural responses to exercise between men and women. Existing research is predominantly observational and limited to racially homogenous populations, which underscores the need for comprehensive studies encompassing diverse, non-White ethnic groups in athlete and non-athlete populations. These individuals exhibit a disproportionately high burden of AF risk factors that could be addressed through improved CRF. Despite the limitations, randomized control trials offer promising evidence for the efficacy of CRF interventions in patients with preexisting AF, showcasing improvements in clinically significant AF outcomes and patient quality of life. The potential of CRF as a countermeasure to the consequences of AF remains an area of great promise, urging future research to delve deeper to explore its role within specific racial and gender contexts. This comprehensive understanding will contribute to the development of tailored strategies for optimizing cardiovascular health and AF prevention in all those who are affected.

Antibiotic Diversity Index: A novel metric to assess antibiotic variation among hospitalized children.

BACKGROUND: Despite nationally endorsed treatment guidelines and stewardship programs, variation and deviation from evidence-based antibiotic prescribing occur, contributing to inappropriate use and medication-related adverse events. Measures of antibiotic prescribing variability can aid in quantifying this problem but are not adequate. OBJECTIVE: The objective of this study is to develop a standardized metric to quantify antibiotic prescribing variability (diversity) within and across children's hospitals, and to examine its association with outcomes. METHODS: We performed a cross-sectional study of empiric antibiotic exposure among children hospitalized during 2017-2019 with one of 15 common pediatric infections using the Pediatric Health Information System database. Encounters for children with complex chronic conditions, transfers in, and birth hospitalizations were excluded. Using the Shannon-Weiner entropy index, we quantified antibiotic diversity for each infection type using the d-measure of diversity. Generalized linear mixed-effects models were used to examine the association between hospital-level antibiotic diversity and risk-adjusted length of stay and costs. RESULTS: A total of 79,515 hospitalizations for common pediatric infections were included. Antibiotic diversity varied within and across hospitals. Infections with low mean antibiotic diversity included appendicitis (mean diversity [mDiv] = 4.9, SD = 2.5) and deep neck space infections (mDiv = 5.9, SD = 1.9). Infections with high mean antibiotic diversity included pneumonia (mDiv = 23.4, SD = 5.6) and septicemia/bacteremia (mDiv = 28.5, SD = 12.1). There was no statistically significant association between hospital-level antibiotic diversity and risk-adjusted LOS or costs. CONCLUSIONS: We developed and applied a novel metric to quantify diversity in antibiotic prescribing that permits comparisons across hospitals and can be leveraged to identify high-priority areas for local and national stewardship interventions.