Cincinnati Children's Hospital Medical Center

“It is surprising that a behavior as subtle and potentially meaningless as one's speech style should affect something as consequential as one's ability to get promoted or be respected.”1 - Deborah Tannen, Talking from 9 to 5: Women and Men at Work Most leaders are taught that effective communication requires confident, decisive (agentic) language, often accompanied by strong body language. This advice is particularly emphasized for women in leadership, who are often assumed to be skilled in displaying warmth and likability, and less so in projecting power. Does this conventional wisdom apply in all circumstances? In a landscape that has become increasingly team-based, healthcare leaders must shift from traditional hierarchical leadership models to collaborative approaches.2 Such a shift calls attention to the difference between power and status. Power is the ability to grant or withhold tangible resources. Many physician leaders, however, lack power in this sense and must influence those they lead via status—a term social scientists use to encompass the respect and regard an individual holds in the eyes of other group members. Unlike power, status cannot be demanded from others: one can have only as much status as others are willing to give. Power and status may coexist, though the holding of power does not automatically confer status, and a person may possess status without power. Despite business literature generally promoting agentic leadership, other research highlights the subtle utility of “power-less” (communal) speech.3 Power-less speech softens one's assertions and orients toward relationship and collaboration. It is characterized by using qualifiers (e.g. “kind of,” “sort of”), adding tag questions (e.g. “don't you think?”), and accompanying statements with disclaimers (“I'm not sure if this will work, but.”). This technique elevates the input of others by conveying that the speaker does not have all the answers. Power-less speech is most useful in settings where tasks and teams are interdependent since groups value traits that prioritize communal aims. Asking open-ended questions builds social capital by empowering the listeners in their own goals and can motivate a team around a shared vision. The complex challenges in healthcare require leaders to shift between communal and agentic language, with skilled leaders recognizing and adapting their communication methods to suit the needs at hand and foster positive change. For example, agentic language may help a division leader cast a leadership vision and strategy for their team. On the other hand, a medical director seeking to improve a quality measure will do well to use communal language to foster dialogue and solicit solutions from all team members. Language has power. It shapes our social realities and relationships. Regardless of gender, minor language adjustments allow leaders to build influence in dynamic, context-dependent work ecosystems. Agentic or powerful language is not inherently bad. In fact, for leaders with minoritized identities, powerful and agentic language is frequently necessary. But consider using power-less language as a status-building approach in situations of high interdependence. Leaders can use language in a manner that is fit for purpose rather than always promoting agentic and powerful language in every situation. The authors would like to thank Dr. Ben Kinnear for his contributions to this piece and his always wonderful sponsorship of others. The authors declare no conflicts of interest.

The study goal was to evaluate the outcomes associated with albumin use in children with sepsis and shock compared with those without shock, using causal inference analysis in a multicenter cohort. This was a secondary analysis of electronic health record data collected from 13 U.S. PICUs between 2012 and 2018, consisting of children younger than 18 years who met Phoenix sepsis criteria within the first 24 hours of PICU admission. Covariate-balancing propensity score weighting was applied to adjust for indication bias in the albumin use. Patients receiving at least 0.5 g/kg albumin within 24 hours of PICU admission were assigned to the albumin group; others to the control. Only 24-hour survivors were included to address immortal time bias. Overall, 17,307 children with sepsis survived at least 24 hours. Of these, 1,344 patients (7.8%) who received albumin within the first 24 hours, and 9,678 (55.9%) met the criteria for septic shock. A significant interaction between albumin use and shock status was observed (interaction: -0.353, p = 0.007), with albumin administration in pediatric septic shock patients associated with lower in-hospital mortality: odds ratio equals to 0.698 (95% CI, 0.629-0.774), risk ratio equals to 0.746 (95% CI, 0.625-0.891), and hazard ratio equals to 0.688 (95% CI, 0.558-0.848). In contrast, there was no difference in outcomes between the albumin and control groups in the non-shock group. Early albumin administration was associated with improved outcomes in children with septic shock, but not in those without shock. These results highlight the importance of considering clinical heterogeneity, such as the presence of shock, in identifying treatment-responsive subgroups and enabling more targeted interventions in pediatric sepsis. Further prospective validation is warranted.

A recurrent de novo germline variant in the MAX gene, p.(Arg60Gln), has recently been associated with polydactyly-macrocephaly syndrome in six unrelated individuals. Affected individuals presented with progressive macrocephaly, post-axial polydactyly, developmental delay, autistic features and a series of craniofacial, brain, cardiac, ocular, and renal anomalies. Here, we describe two unrelated female probands with the known recurrent MAX variant, c.179G>A p.(Arg60Gln), who presented with the emerging phenotypes of the MAX-associated syndrome. We also propose that genitourinary abnormalities, including Mayer-Rokitanski-Kuster-Hauser syndrome in one individual, may constitute an expansion of the known phenotype. These findings contribute to the current knowledge regarding the phenotypic spectrum of MAX-associated polydactyly-macrocephaly syndrome.

Humans with pathogenic loss of function alanyl-tRNA synthetase 1 (AARS1) variants have a range of congenital brain phenotypes, including a high prevalence of microcephaly. The molecular mechanisms for this are unclear but zebrafish mutants in aars1 have reduced neurogenesis and increased apoptosis. Here, we report two individuals with compound heterozygous AARS1 variants. We created two mouse models to study the role of Aars1 in embryonic brain development. We provide evidence from these mouse models and in vitro splicing assays that both human AARS1 alleles are pathogenic. Mice homozygous for either a missense allele or an indel allele are both lethal very early in embryonic development. Aars1G80S/WT heterozygous animals show reduced Purkinje cell immunoreactivity at 8 months of age but no gross morphological cerebellar phenotypes or impaired performance in a motor coordination assay. We conclude these are pathogenic alleles in AARS1 but lethality in mice preclude a detailed study of neural development.

Outcomes for pediatric relapsed/refractory (R/R) acute myeloid leukemia (AML) remain dismal. CPX-351, a liposomal formulation of cytarabine and daunorubicin, may have less off-target toxicities than traditional chemotherapies and has shown improved outcomes for adults with newly diagnosed therapy-related AML. In this first-in-pediatric, single center phase 1 study (NCT01943682), 27 patients with R/R acute leukemia (acute lymphoblastic leukemia [ALL, n = 3], AML [n = 23], or mixed phenotype acute leukemia [MPAL, n = 1]) received one cycle of CPX-351 (on days 1, 3, 5) at either 44mg/m2 daunorubicin/dose or 59mg/m2 daunorubicin/dose. The primary objectives were to determine the CPX-351 recommended phase 2 dose (RP2D) and to evaluate its tolerability; secondary objectives were to assess marrow overall response rate (ORR) and cardiotoxicity. The RP2D was determined to be 44mg/m2 daunorubicin/dose. Grade ≥3 non-hematologic toxicities occurred in 89% of patients including febrile neutropenia (85%), infection (52%), and maculo-papular rash (37%). No grade ≥3 acute cardiac toxicities or significant changes in cardiac biomarkers were detected. The marrow ORR for AML patients was 48% (10/21 evaluable patients), despite high-risk genetic findings in most and nearly half of patients having undergone prior hematopoietic stem cell transplant. No patients with ALL or MPAL responded. CPX-351 at 44mg/m2 daunorubicin/dose was safe and tolerable in children with R/R acute leukemia, showing promising activity in heavily pretreated, high-risk AML and is now the FDA-approved pediatric dose for therapy-related AML or AML with myelodysplastic changes.