Faculty Bibliography

Families of infants hospitalized in the neonatal intensive care unit (NICU) are at an increased risk for depression, anxiety, and trauma symptoms that often persist well beyond transition from the NICU. While NICU professionals provide vital medical care for high-risk infants, they also offer interdisciplinary support for families, including collaboration with psychosocial and psychiatric services in select settings. Despite psychosocial support systems often being present during NICU hospitalization, significant gaps remain in post-NICU mental health support for parents. Comprehensive discharge preparation and outpatient follow-up planning for infants, as well as their families, are essential to optimize both long-term outcomes and the well-being of the entire family unit. In this paper, we review current evidence regarding mental health risks for families during transitions of care and highlight practice recommendations and advocacy opportunities for enhanced family-centered, interdisciplinary follow-up care after transition from the NICU.

BACKGROUND:ASH1L-related intellectual developmental disorder represents an emerging neurodevelopmental syndrome with significant phenotypic heterogeneity (Cordova et al. in Genes (Basel). 15(4):423, 2024). Comprehensive genomic analysis demonstrates superior diagnostic yield compared with targeted approaches in complex neurodevelopmental presentations (Srivastava et al. in Genet Med. 21(11):2413-2421, 2019). CASE PRESENTATION/METHODS:This report describes a 6-year-old Central Asian (Uzbek) male patient with a history of global developmental delay who was diagnosed with mild autism spectrum disorder, attention-deficit/hyperactivity disorder, and a developmental expressive language disorder. Neuropsychological assessment revealed an uneven cognitive profile with average verbal abilities but below-average nonverbal reasoning. After uninformative targeted genetic panels, trio whole-genome sequencing identified a novel de novo heterozygous missense variant in ASH1L c.4043A > G (p.Lys1348Arg). This variant, absent in population databases, was classified as a variant of uncertain significance. However, in silico analysis predicted this variant to be probably damaging, and therefore, it emerged as the strongest candidate to explain the patient's phenotype. CONCLUSION/CONCLUSIONS:This case expands the known phenotypic spectrum of ASH1L-related disorders, demonstrating that a de novo missense variant can be associated with a milder neurodevelopmental phenotype, including borderline-to-average intellectual ability. These findings challenge suggestions that missense variants uniformly lead to more severe outcomes and underscores the importance of comprehensive genomic and deep clinical characterization to refine our understanding of gene-disease relationships.

The kidneys contribute to glucose homeostasis by gluconeogenesis and glucose reabsorption. Herein, we identified previously unknown fasting-induced, glucagon-mediated inhibitory effect of the circadian clock gene basic helix-loop-helix ARNT like 1 (Bmal1) on the expression of the main proximal tubule glucose transporter solute carrier family 5 member 2 (Sglt2) in mice. During fasting, glucagon induces Bmal1, which increases expression of nuclear receptor subfamily 1, group D, member 1 (Rev-erbα). Rev-erbα represses nuclear respiratory factor 1, a transcriptional activator of Sglt2, and diminishes Sglt2 expression and thereby kidney glucose reabsorption capacity. During refeeding (lower glucagon) this process is attenuated, thereby inducing glucose reabsorption. The physiological role of this mechanism appears to ensure optimal temporal retrieval of filtered glucose during fasting/refeeding. Thus, this study demonstrates that during fasting and refeeding, glucagon regulates renal glucose reabsorption by utilizing the local cellular circadian machinery.

HOXB13 is a prostate-specific transcription factor best known for its role as an androgen receptor (AR) cofactor. Recent evidence suggests that HOXB13 plays critical AR-independent functions in repressing lipogenic programs and promoting prostate cancer (PCa) metastasis. However, the mechanisms linking HOXB13 loss to tumor metastasis remain unclear. Here, we show that p300 and CBP co-occupy lipogenic enhancers suppressed by HOXB13 and HDAC3 and are essential for enhancer activation and target gene expression following HOXB13 depletion. Loss of HOXB13 induces lipid-sensitive matrix metalloproteinases (MMPs), promoting increased cell motility. Importantly, pharmacological inhibition of p300 and CBP blocks HOXB13-loss-driven lipogenesis, reduces MMP expression, and decreases cell migration in vitro and tumor metastasis in vivo. Analysis of clinical samples revealed that HOXB13 expression is reduced in metastatic hormone-sensitive PCa compared with matched primary tumors, further supporting its role in tumor metastasis. These findings demonstrate that HOXB13 downregulation promotes PCa metastasis through p300- and CBP-dependent lipogenic and motility pathways, which may be targeted by p300 inhibition.

BACKGROUND:This study assessed whether there is a correlation between the grade of splenic injury and the semiquantitative assessment of the amount of the hemoperitoneum (HP) by a modified Federle score (mFS), and which of the 2 factors is more predictive of the need for intervention in adult patients with isolated blunt splenic injury (iBSI). METHODS:Retrospective cohort study of patients admitted (1/1/2019-12/31/2022) with iBSI. Continuous data are presented as means ± standard deviation and non-parametric data as frequencies with percentages. A test-retest analysis for intra- and inter-class reliability of HP assessment was done in a 10-patient subgroup. RESULTS:Among the 62 patients, 47 (75.8%) were managed nonoperatively (23 observation, 24 splenic artery embolization [SAE]), and 15 underwent splenectomy. The grade of splenic injury and mFS scores were 3.6 ± 1.3 and 4.1 ± 1.9, respectively. The 22 patients who underwent SAE were more severely injured in terms of grade of splenic injury (4.0 ± 1.2 vs 2.6 ± 1.1), amount of HP by mFS (4.1 ± 1.8 vs 3.1 ± 1.7) and ISS (21 ± 11 vs 15 ± 12) compared to the observed patients (P < .05). Mortality was 8%. SAE and splenectomy groups differed only by the quantity of HP (4.1 ± 1.8 vs 5.5 ±1.3). While there was a correlation between AAST grade and mFS, only mFS was predictive of splenectomy. CONCLUSION/CONCLUSIONS:The quantity of HP as assessed by mFS may be more predictive than the grade of splenic injury regarding the need for splenectomy in patients with iBSI.

PURPOSE/OBJECTIVE:Chemotherapy-induced alopecia (CIA) affects approximately 65% of patients receiving chemotherapy and has a negative impact on quality of life (QoL). Scalp cooling (SC) is the only FDA-cleared intervention for CIA. This systematic review and meta-analysis evaluated SC adverse events (AEs), reasons for discontinuation, and scalp metastasis incidence. METHODS:Meta-analyses using random-effects models estimated pooled prevalences of SC AEs, SC discontinuation, and reasons for discontinuation. A generalized linear mixed model was used to estimate the incidence of scalp metastasis. RESULTS:Sixty-seven studies met the inclusion criteria. The most common AEs were generalized chills (42%, 95% confidence interval (CI) 26-58%), cap heaviness (35%, 95% CI 18-52%), and headache (30%, 95% CI 21-39%). The SC discontinuation rate was 18% (95% CI 13-23%). The most common reasons for discontinuation were progressive alopecia (15%, 95% CI 10-20%) and reasons unrelated to SC (9%, 95% CI 5-13%). The most frequent AEs leading to SC discontinuation were headache (4%, 95% CI 2-6%), cold intolerance (4%, 95% CI 3-5%), and general discomfort (4%, 95% CI 2-7%). Secondary analysis of scalp metastases yielded an incidence of 0.15% (95% CI 0.05-0.47%). Analysis of FDA Manufacturer and User Facility Device Experience (MAUDE) database medical device reports revealed that user error contributed to cold thermal injuries. Prevalence estimates were limited by significant heterogeneity between studies, reflecting variations in study methodology and real-world SC practices. CONCLUSION/CONCLUSIONS:SC is generally well tolerated with minimal safety concerns. Clinical comfort strategies like supportive medications and improved patient education could enhance SC tolerability and support its implementation.

Efficient recycling of red blood cells (RBCs) requires not only heme cleavage but also stabilization of reactive intermediates generated during iron liberation. Lipocalin Prostaglandin D₂ Synthase (L-PGDS, β-trace protein), best known for prostaglandin synthesis, possesses structural and biochemical features consistent with a buffering role in heme catabolism. Here, we show that L-PGDS knockout mice exhibit elevated plasma, increased total splenic iron, reduced total hepatic iron, decreased plasma free heme/hemin, and modest RBC enlargement, consistent with disrupted iron release. Transcript-protein mismatches in key iron regulators, including NRF2 and FPN, further suggest redox imbalance and impaired iron sensing. Despite normal Hmox1 expression, these mice display widespread evidence of inefficient porphyrin clearance. Combined with prior findings that L-PGDS binds ferric biliverdin and is upregulated during heme overload, our results support a model in which L-PGDS buffers porphyrin intermediates to facilitate their safe processing and clearance. This study identifies L-PGDS as a putative auxiliary factor in heme catabolism, with implications for iron recycling, erythropoiesis, and systemic iron homeostasis. All data in this report are from male mice.

Rapid molecular assays guiding treatment of methicillin-resistant Staphylococcus aureus (MRSA) detect SCCmec (Xpert) or the SCCmec-orfX junction (BCID2). Sequence variation in this region can disrupt primer binding, yielding false-negative results. Investigation of a missed bloodstream infection linked escape to a CRISPR-Cas-associated SCCmec variant, leading to identification of 64 variants from 45 patients-2% of 2,432 screened. Misdiagnosis was restricted to clonal complex 5, a hospital-associated lineage; 11 of 40 SCCmec/junctions evaded detection by BCID2 or Xpert. Variants had mecA instability and circulated in healthcare settings. Our findings reveal a unique escape mechanism and underscore a threat to diagnostic accuracy.