Increased platelet to red blood cell transfusion ratio associated with acute kidney injury in children with life-threatening bleeding.

INTRODUCTION: Transfusion may increase the risk of organ failure through immunomodulatory effects. The primary objective of this study was to assess for patient or transfusion-related factors that are independently associated with the risk of acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in a cohort of children with life-threatening bleeding from all etiologies. METHODS: In a secondary analysis of the prospective observational massive transfusion in children (MATIC) study, multivariable logistic regression was performed in an adjusted analysis to determine if blood product ratios or deficits were independently associated with AKI or ARDS in children with life-threatening bleeding. RESULTS: There were 449 children included with a median (interquartile range, IQR) age of 7.3 years (1.7-14.7). Within 5 days of the life-threatening bleeding event, AKI occurred in 18.5% and ARDS occurred in 20.3% of the subjects. Every 10% increase in the platelet to red blood cell transfusion ratio is independently associated with a 12.7% increase in the odds of AKI (adjusted odds ratio 1.127; 95% confidence interval 1.025-1.239; p-value .013). Subjects with operative or medical etiologies were independently associated with an increased risk of AKI compared to those with traumatic injury. No transfusion-related variables were independently associated with the risk of developing ARDS. CONCLUSION: The use of increased platelet to red blood cell transfusion ratios in children with life-threatening bleeding of any etiology may increase the risk of AKI but not ARDS. Prospective trials are needed to determine if increased platelet use in this cohort increases the risk of AKI to examine possible mechanisms.

Indoximod-based chemo-immunotherapy for pediatric brain tumors: A first-in-children phase I trial.

BACKGROUND: Recurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy. METHODS: We conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for indoximod in combination with oral temozolomide (200 mg/m2/day x 5 days in 28-day cycles), or with palliative conformal radiation. Blood samples were collected at baseline and monthly for single-cell RNA-sequencing with paired single-cell T cell receptor sequencing. RESULTS: Eighty-one patients were treated with indoximod-based combination therapy. Median follow-up was 52 months (range 39-77 months). Maximum tolerated dose was not reached, and the pediatric dose of indoximod was determined as 19.2 mg/kg/dose, twice daily. Median overall survival was 13.3 months (n = 68, range 0.2-62.7) for all patients with recurrent disease and 14.4 months (n = 13, range 4.7-29.7) for DIPG. The subset of n = 26 patients who showed evidence of objective response (even a partial or mixed response) had over 3-fold longer median OS (25.2 months, range 5.4-61.9, p = 0.006) compared to n = 37 nonresponders (7.3 months, range 0.2-62.7). Four patients remain free of active disease longer than 36 months. Single-cell sequencing confirmed emergence of new circulating CD8 T cell clonotypes with late effector phenotype. CONCLUSIONS: Indoximod was well tolerated and could be safely combined with chemotherapy and radiation. Encouraging preliminary evidence of efficacy supports advancing to Phase II/III trials for pediatric brain tumors.

First Case of a Term Male Born with Aphallia and Complete Urethral Atresia.

Aphallia is an exceedingly rare condition often associated with an array of genitourinary anomalies. Classically, aphallia was thought to have to co-exist with a urethral fistula for adequate urine outflow to avoid the sequelae of oligohydramnios, while the absence of a fistula has historically been incompatible with life. We report the first case of a prenatally unrecognized aphallia with complete urethral atresia in a full-term baby, without an associated fistula or ectopic urethra. We postulate a urachal cyst noted on prenatal ultrasound resolved into a patent urachus providing sufficient outflow to avoid sequelae of oligohydramnios and allowed for term birth.

Rare case: Ureteropelvic junction complication presenting with bilateral labial abscesses and urosepsis requiring nephrectomy.

Ureteropelvic junction obstruction (UPJO) is the most common cause of urinary tract obstruction in pediatric patients. Debates in management include ureteral stent versus nephrostomy tube placement prior to surgical correction if intervention is warranted. We present a female patient with left UPJO, diagnosed at 15-years-old, treated with ureteral stent placement. Stent removal two years later resulted in extensive complications, including retroperitoneal infection, labial abscesses, and nephrectomy. Management of UPJO in the pediatric population prior to surgical correction is not well-standardized. The severity of complications following the removal of the two-year-old stent suggests caution for placing ureteral stents without proper follow-up.

What does it mean to be a physician? Exploring social imaginaries of first-year medical students.

OBJECTIVES: To explore if community embedded discussions with local community members reshape the social imaginary of medicine among students and contribute positively to their professional identity. METHODS: This explorative, qualitative study involved 35 first-year medical students who volunteered to attend a 2-hour forum at a local church to ask community members about their experiences with doctors and healthcare systems.  Student participants were asked to reflect on five structured questions. The written reflections were submitted for analysis, de-identified, and analyzed using Glaser's classic grounded theory, constant comparative analysis, and Taylor's model of modern social imaginaries as an analytical lens. RESULTS: The results indicate that student participants identified seven main themes regarding what community members expect from their doctors, including active listening (n=22), physical touch (n=18), and compassion (n=16). Responses also indicated that only 5.6% of the students felt that the preclinical curriculum was adequately preparing them for what local community members identified as important to patient care. However, students recognized that two aspects of the curriculum, Physical Diagnosis (n=12) and volunteering/community engagement (n=9), were congruent with the expectations of future patients. CONCLUSIONS: The results suggest that students identified educational experiences that were congruent with the social imaginary of patients. However, patient expectations were discordant to some aspects of the medical imaginary of medical students. The experience and subsequent reflections may be salient to contributing to each student's professional identity and provide a model for other medical schools to explore how the curriculum is fulfilling the community's perception of ideal patient care.