Publications by Year: 2026

BACKGROUND CONTEXT: Optimizing the surgical episode cost of care represents a major opportunity for healthcare cost reduction. This requires determining an accurate estimate of these costs, which has historically been difficult to determine. Time-driven activity-based costing (TDABC) has emerged as a methodology for determining more accurate surgical cost drivers compared to traditional methods.

PURPOSE: To examine cost variation and cost drivers in single-level lumbar discectomies using TDABC methodology, focusing on total hospital cost variation, differences between high- and nonhigh-cost patients and identification of main factors affecting total hospital cost.

STUDY DESIGN/SETTING: Retrospective, multicenter, observational study conducted at an integrated healthcare system between November 2021 and December 2022.

PATIENT SAMPLE: The cohort comprised 184 patients undergoing isolated, primary single-level lumbar or lumbosacral discectomy. Revision procedures, multilevel surgeries, concurrent procedures, and cases performed by surgeons with fewer than nine procedures were excluded.

OUTCOME MEASURES: Total hospital costs were calculated using TDABC methodology and normalized to an average of 1.00 per institutional requirements. Cost variation, cost drivers, and differences between high-cost (top decile) and nonhigh-cost patients were assessed.

METHODS: TDABC methodology was utilized to calculate total costs for all procedures. Statistical analyses included descriptive statistics, bivariate comparisons between high-cost and nonhigh-cost patients, and multivariable linear regression to identify individual cost drivers.

RESULTS: The most expensive surgery was 3.6 times more expensive than the least expensive, with intraoperative costs comprising 79% of total expenses. A strong correlation existed between surgical time and total cost (ρ=0.78, p<.001). High-cost patients were more likely to undergo surgery at academic medical centers (89% vs. 42%, p<.001), less likely to have outpatient surgery (33% vs. 93%, p<.001), had a higher comorbidity burden (Elixhauser comorbidity index 3.1 vs. 1.7, p=.005), and longer operative times (153 vs. 59 minutes, p<.001). Multivariable analysis identified surgical time, outpatient surgery, surgery location, and individual surgeon idiosyncrasies as significant cost determinants.

CONCLUSIONS: Single-level lumbar discectomies demonstrate modest cost variation primarily driven by surgical time, patient complexity, and surgeon-specific factors. While efforts to reduce unwarranted cost variation without negatively impacting patient outcomes are warranted, orthopedic or neurosurgical departments and hospital systems may wish to focus their initial efforts on higher cost spine procedures with greater cost variation first before tackling single-level lumbar discectomies.

Anaplastic lymphoma kinase (ALK) rearrangements have emerged as a defining molecular alteration across a wide spectrum of cutaneous mesenchymal and melanocytic neoplasms with diverse clinical, histologic, immunophenotypic, and biologic features. This article describes several distinct ALK-rearranged cutaneous neoplasms: epithelioid fibrous histiocytoma, superficial ALK-rearranged myxoid spindle cell neoplasm, nonneural granular cell tumor, Spitz melanocytic neoplasms, and other emerging entities. ALK overexpression by immunohistochemistry and confirmatory molecular testing, when necessary, plays a critical diagnostic role. The expanding spectrum of ALK-rearranged cutaneous tumors underscores the value of an integrated diagnostic approach to ensure accurate diagnosis and guide clinical management.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive form of acute leukemia. BPDCN has a strong predilection for the skin and poses diagnostic challenges with clinical and histologic features that overlap with other conditions. BPDCN shows recurrent myeloid-associated mutations, complex chromosomal aberrancies, and copy-number changes with chromosomal losses involving tumor suppressors and cell cycle regulators. In patients with cutaneous BPDCN, the bone marrow frequently harbors mutationally related myeloid clones/neoplasms; BPDCN transforms from underlying premalignant hematopoietic clones with acquisition of additional progression events, and often occurs in association with ultraviolet damage in sun-exposed sites.

Microcirculatory dysfunction plays a central role in sepsis pathophysiology and is associated with poor clinical outcomes. While advances in bedside tools and biomarkers offer potential for identifying microcirculatory dysfunction, most therapies targeting the microcirculation have not translated into improved clinical outcomes. Future advances likely lie in precision medicine approaches that employ microcirculatory measurements to guide individualized resuscitation strategies. This article highlights current evidence on the physiology, assessment, and therapeutic approaches to microvascular dysfunction in sepsis, underscoring the need for precision medicine strategies and further research into patient subgroups that may benefit from microcirculation directed interventions.

The burden of sepsis is poorly understood, but it is estimated that nearly 50 million cases of sepsis occur annually, accounting for nearly 20% of all deaths globally. Modern techniques to capture sepsis epidemiology are limited, particularly when applied to lower-middle income countries where the burden of sepsis is highest. We need more robust data sets, surveillance infrastructure, and integrated research to better assess the prevalence of this syndrome, identify vulnerable populations, and develop policy interventions to effectively mitigate the impact of sepsis globally.

BACKGROUND: Clozapine is highly effective for treatment-resistant schizophrenia but has been associated with an increased risk of agranulocytosis. As a result, until 2025, the Food and Drug Administration required patients receiving clozapine to undergo regular blood testing to monitor for neutropenia as part of a Risk Evaluation and Mitigation Strategy (REMS) programme.

OBJECTIVE: This study sought to compare the risk of neutropenia-related hospitalisations between clozapine and olanzapine initiators.

METHODS: The study cohort was nested in claims data from Medicaid and two commercial health insurance databases and consisted of adults initiating clozapine or olanzapine who had a recorded diagnosis of schizophrenia or schizoaffective disorder and ≥1 dispensing of a different antipsychotic in the 6 months before initiation. Propensity score matching (1:1) was used to mitigate confounding. The primary outcome was hospitalisation with a neutropenia diagnosis in the primary position. Both as-treated and intention-to-treat analyses were implemented.

FINDINGS: After propensity score matching, there were 16 873 initiators in each group. At 6 months postinitiation, there were 12 neutropenia-related hospitalisations among the clozapine cohort (incidence rate: 2.21 per 1000 person-years; 95% CI 1.25 to 3.89) and <11 among the olanzapine cohort (0.18; 95% CI 0.03 to 1.29), corresponding to an incidence rate ratio (IRR) of 12.18 (95% CI 1.58 to 93.71). The IRRs were 5.77 (95% CI 1.29 to 25.76) at 1 year, 5.50 (95% CI 1.23 to 24.55) at 2 years and 5.40 (95% CI 1.21 to 24.13) at 3 years postinitiation. Associations remained but were attenuated in intention-to-treat analyses.

CONCLUSIONS: Clozapine initiators had an elevated risk of neutropenia-related hospitalisation, especially during the first 6 months of treatment, although the absolute risk was low.

CLINICAL IMPLICATIONS: Despite removal of the REMS programme, it is important for prescribers to monitor patients for neutropenia after initiating clozapine.

BACKGROUND: Premature birth is the leading cause of neonatal morbidity and mortality. Understanding perceptions, beliefs and attitudes towards preterm births, and how these factors influence care provision at health facilities and at home is crucial for improving preterm newborns' health outcomes.

METHODS: We conducted an exploratory qualitative study at Batu and Meki communities in the East Shewa Zone of Oromia Region, Ethiopia. We conducted in-depth interviews (n=81) and focus group discussions (n=8) using semistructured guides. The study participants included women who had preterm births, family members, community members, healthcare workers and expert stakeholders. We audio-recorded, transcribed the interviews and coded the transcripts. We employed the socioecological model to present perceptions, beliefs and attitudes towards preterm birth at individual, interpersonal, organisational and societal levels.

FINDINGS: Giving birth to a preterm newborn is often associated with fear, stress, unhappiness, concern and worry. At the individual level, preterm newborns' mothers often feel guilt and self-blame. Families tend to keep preterm birth a secret due to perceptions of 'incompleteness'. At the interpersonal level, preterm newborns are often stigmatised and families are disappointed by mothers who give birth prematurely. However, some believe that preterm newborns are accepted within the community. At the organisational level, healthcare providers find the causes of preterm birth unpredictable, they do not consider preterm births prevalent, and consider some of them as abortion. There is also a common belief that preterm infants have a low survival rate, leading to the deprioritisation of their care. At the societal level, some believe preterm births are caused by divine will as punishment for sins committed by the mother, while others think they occur naturally. Preterm newborn's death is often not acknowledged as true loss and families are discouraged from grieving.

CONCLUSIONS: Our study found that the beliefs, perceptions and attitudes surrounding preterm birth, held by families, communities, healthcare providers and society at large, influence the care that preterm newborn-mother dyads receive both at home and within health facilities. Addressing these requires a multifaceted approach targeted at deeply ingrained attitudes and perceptions.

Eosinophilic lung diseases (ELDs) represent a heterogeneous group of airway and parenchymal disorders unified by eosinophilic inflammation but distinguished by diverse clinical features, mechanisms of persistence, and variable therapeutic responses. Traditional diagnostic tools, including blood eosinophil counts, bronchoalveolar lavage, sputum cytology, and exhaled nitric oxide, predict the eosinophilic/T2 burden of the disease but often fail to distinguish IL-5-dependent from IL-5-independent pathways, overlook compartment-specific inflammation, and inadequately predict or monitor response to targeted biologics. The inconsistent efficacy of IL-5/IL-5R-directed monoclonal antibodies despite normalization of blood eosinophils across the ELD spectrum (robust clinical response in eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome, partial in asthma and largely absent in chronic obstructive pulmonary disease) underscores the limitations of current biomarkers and the need for refined precision endotyping. To address these gaps, emerging biomarker platforms move beyond eosinophil enumeration to define upstream drivers, activation states, tissue localization, and immune pathways sustaining persistent eosinophilia. These advances include noninvasive tools such as lateral-flow devices for assaying eosinophil peroxidase (eosinophil activity biomarker), breathomics and volatile organic compound profiling, cytokine-level inflammatory mapping, and composite biomarker models integrating airway, blood, and molecular signatures. In parallel, functional imaging modalities, including hyperpolarized gas magnetic resonance imaging, phase-resolved functional lung magnetic resonance imaging, and quantitative computed tomography, provide noninvasive, high-resolution visualization of regional ventilation, perfusion, and inflammation. This enables clinicians to look into the lungs and offer powerful stand-alone or complementary biomarker capability. Collectively, these innovations mark a shift toward mechanistically-informed, tissue-specific, multimodal biomarker strategies that refine diagnosis, improve therapeutic selection, and enhance monitoring across the ELD spectrum, advancing the promise of precision medicine.

BACKGROUND: Human milk (HM) contains bioactive constituents that continuously change throughout lactation and that are critical for optimal infant development. However, the temporal variation of the HM metabolome, its maternal nutritional determinants, and its links to infant outcomes remain insufficiently characterized in low-middle-income countries (LMIC) where childhood disease burden and HM exposure are substantial, and maternal nutritional status is poor.

OBJECTIVES: We aimed to 1) characterize temporal changes in the HM metabolome, 2) quantify maternal nutritional status-related differences in HM metabolomic patterns, and 3) determine whether HM metabolomic patterns associated with maternal nutritional status are in turn associated with infant growth, in a cohort of rural Bangladeshi maternal-infant dyads.

METHODS: In a lactation cohort (n = 99, 6% preterm at 34-36 wk), we characterized metabolites in HM samples at 2 (n = 94) and 5 (n = 88) mo postpartum (PP) using untargeted metabolomics profiling. We performed a paired t-test to identify metabolites that differed between timepoints and principal component analysis to consolidate metabolites measured at each timepoint into "factors," representing metabolite patterns. We used linear regression models to determine associations between maternal nutritional predictors, factor scores at 2 and 5 mo, and infant growth outcomes, and performed metabolite set enrichment analysis (MSEA) to characterize relevant pathways. P values were adjusted for multiple comparisons.

RESULTS: Among the 51 metabolites that differed in relative abundance across the 2 time points, 37 (73%) metabolites decreased over time, mainly comprising lipids (sphingolipids and phospholipids), and amino acids (AA). MSEA did not reveal specific metabolic pathway alterations over time. HM from mothers in the highest (compared with middle, ref) body mass index (BMI) tertile PP had significantly lower scores for a metabolomic pattern (factor 5) characterized by AA that enriched in 6 critical metabolic pathways (metabolism of glutathione, glutamate, alanine, glycine and serine, and aspartate; and the ammonia recycling pathway). In turn, lower scores for this profile were associated with greater (β = 0.22; 95% confidence interval: 0.00, 0.43) infant weight-for-age z-score at 3 mo but not 6 mo. Additionally, HM from undernourished mothers had lower scores for a metabolomic pattern (factor 4) characterized mainly by AA and acylcarnitines involved in branched chain AA and fatty acids metabolism, although MSEA were not significant. This pattern was not associated with infant growth.

CONCLUSIONS: In this LMIC cohort, the abundance of several lipid and AA metabolites declined over time. Furthermore, HM metabolome differences in mothers with high BMI may underpin early weight gain in their infants. More studies from LMICs are needed to understand maternal nutrition-driven differences in HM composition that may impact infant growth and development to guide interventions in these high-risk breastfeeding populations.